Pyridodiazines as plant fungicides

ABSTRACT

Fungicidal compounds of general formula (1) wherein R, R 1 , R 2 , W, X, Y and Z are as defined in the specification.

This invention relates to novel derivatives of pyridopyrazines andpyridopyridazines, to processes for preparing them, to certainintermediate chemicals used in their manufacture, to compositionscontaining them and to methods of using them to combat fungi, especiallyfungal infections of plants.

Derivatives of the nitrogen-containing 5,6 ring systems-1,2,4-triazolo[1,5-a]pyrimidine are known from the patent literatureas being useful for controlling phytopathogenic fungi. Examples ofrecent patent publications include EP-A-1249452, WO 02/051845, WO02/083676, WO 02/083677, WO 02/088125, WO 02/088126, WO 02/088127.Derivatives of pyridopyrazines are known in the chemical literature, forexample from J. Med. Chem. (1968), 11(6), 1216-18, J. Med. Chem. (1970),13(5), 853-7 and U.S. Pat. No. 3,984,412, but not for agrochemicalpurposes.

The present invention is concerned with the provision of novelpyridopyrazines and pyridopyridazines for combating phytopathogenicdiseases on plants and harvested food crops.

Thus, according to the present invention, there is provided a compoundof the general formula (1):

whereinW and X, W and Z, X and Y or Y and Z are N and the other two are CR⁸;R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl;R and R² are independently H, halo, C₁₋₈ alkyl, C₁₋₈ alkoxy, C₁₋₈alkylthio, C₂₋₈ alkenyl, C₂₋₈ alkynyl, cyano or NR³R⁴, provided that atleast one of R and R² is NR³R⁴;R¹ is halo, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, C₃₋₈ cycloalkyl,C₃₋₈ cycloalkyl(C₁₋₆)alkyl, C₁₋₈ alkoxy, C₁₋₈ alkylthio, aryl, aryloxy,arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(C₁₋₄)alkyl,aryl(C₁₋₄)alkoxy, heteroaryl(C₁₋₄)alkyl, heteroaryl(C₁₋₄)alkoxy,aryl(C₁₋₄)-alkylthio, heteroaryl(C₁₋₄)alkylthio, morpholino, piperidinoor pyrrolidino;R³ and R⁴ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl,aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl,heteroaryl, heteroaryl(C₁₋₈)alkyl, NR⁵R⁶, provided that not both R³ andR⁴ are H or NR⁵R⁶, orR³ and R⁴ together form a C₃₋₇ alkylene or C₃₋₇ alkenylene chainoptionally substituted with one or more C₁₋₄ alkyl or C₁₋₄ alkoxygroups, or,together with the nitrogen atom to which they are attached, R³ and R⁴form a morpholine, thiomorpholine, thiomorpholine S-oxide orthiomorpholine S-dioxide ring or a piperazine or piperazineN—(C₁₋₄)alkyl (especially N-methyl) ring; andR⁵ and R⁶ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl,aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl,heteroaryl or heteroaryl(C₁₋₈)alkyl;any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups ormoieties (other than for R⁸) being optionally substituted with halogen,cyano, C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxycarbonyl, C₁₋₆haloalkoxy, C₁₋₆ alkylthio, tri(C₁₋₄)alkylsilyl, C₁₋₆ alkylamino or C₁₋₆dialkylamino,any of the foregoing morpholine, thiomorpholine, piperidine, piperazineand pyrrolidine rings being optionally substituted with C₁₋₄ alkyl(especially methyl), andany of the foregoing aryl or heteroaryl groups or moieties beingoptionally substituted with one or more substituents selected from halo,hydroxy, mercapto, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ alkoxy,C₂₋₆ alkenyloxy, C₂₋₆ alkynyloxy, halo(C₁₋₆)alkyl, halo(C₁₋₆)alkoxy,C₁₋₆ alkylthio, halo(C₁₋₆)alkylthio, hydroxy(C₁₋₆)alkyl, C₁₋₄alkoxy(C₁₋₆)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenoxy,benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato,nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″, —CONR′″R″″, —SO₂R′″, —OSO₂R′″,—COR′″, —CR′″═NR″″ or —N═CR′″R″″, in which R′″ and R″″ are independentlyhydrogen, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy, halo(C₁₋₄)alkoxy,C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenyl orbenzyl, the phenyl and benzyl groups being optionally substituted withhalogen, C₁₋₄ alkyl or C₁₋₄ alkoxy.

The invention includes a compound of the general formula (1) as definedimmediately above except that: C₁₋₈ alkoxy and C₁₋₈ alkylthio areexcluded as values of R and R²; C₇ alkylene and C₃₋₇ alkenylene areexcluded as chains formed by R³ and R⁴; the C₃₋₆ chain that R³ and R⁴may form may only be optionally substituted with one or more methylgroups; thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxideand piperazine are excluded as rings that R³ and R⁴ may form;tri(C₁₋₄)alkylsilyl is excluded as a substituent of any alkyl, alkenyl,alkynyl or cycloalkyl group or moiety and any morpholine, piperidine orpyrrolidine ring is unsubstituted.

The compounds of the invention may contain one or more asymmetric carbonatoms and may exist as enantiomers (or as pairs of diastereoisomers) oras mixtures of such. They may also exist as diastereoisomers by virtueof restricted rotation about a bond. However, mixtures of enantiomers ordiastereoisomers may be separated into individual isomers or isomerpairs, and this invention embraces such isomers and mixtures thereof inall proportions. It is to be expected that for any given compound, oneisomer may be more fungicidally active than another.

Except where otherwise stated, alkyl groups and alkyl moieties ofalkoxy, alkylthio, etc., contain from 1 to 8, suitably from 1 to 6 andtypically from 1 to 4, carbon atoms in the form of straight or branchedchains. Examples are methyl, ethyl, n- and iso-propyl, n-, sec-, iso-and tert-butyl, n-pentyl and n-hexyl. Cycloalkyl groups contain from 3to 8, typically from 3 to 6, carbon atoms and include bicycloalkylgroups such as the bicyclo[2.2.1]heptyl group. Haloalkyl groups ormoieties are typically trichloromethyl or trifluoromethyl or contain atrichloromethyl or trifluoromethyl terminal group.

Except where otherwise stated, alkenyl and alkynyl moieties also containfrom 2 to 8, suitably from 2 to 6 and typically from 2 to 4, carbonatoms in the form of straight or branched chains. Examples are allyl,2-methylallyl and propargyl. Optional substituents include halo,typically fluoro. An example of halo-substituted alkenyl is3,4,4-trifluoro-n-butenyl.

Halo includes fluoro, chloro, bromo and iodo. Most commonly it isfluoro, chloro or bromo and usually fluoro or chloro.

Aryl is usually phenyl but also includes naphthyl, anthryl andphenanthryl.

Heteroaryl is typically a 5- or 6-membered aromatic ring containing oneor more O, N or S heteroatoms, which may be fused to one or more otheraromatic or heteroaromatic rings, such as a benzene ring. Examples arethienyl, furyl, pyrrolyl, isoxazolyl, oxazolyl, oxadiazolyl, pyrazolyl,imidazolyl, triazolyl, isothiazolyl, tetrazolyl, thiadiazolyl, pyridyl,pyrimidinyl, pyrazinyl, pyridazinyl, triazinyl, benzofuryl,benzothienyl, dibenzofuryl, benzothiazolyl, benzoxazolyl,benzimidazolyl, indolyl, quinolinyl and quinoxalinyl groups and, whereappropriate, N-oxides thereof.

The 6,6-ring systems embraced by the general formula (1) arepyrido[2,3-c]pyridazines (where W and X are both CR⁸ and Y and Z areboth N), pyrido[2,3-d]pyridazines (where W and Z are both CR⁸ and X andY are both N), pyrido[3,2-c]pyridazines (where Y and Z are both CR⁸ andW and X are both N) and pyrido[2,3-b]pyrazine (where X and Y are bothCR⁸ and W and Z are both N). Of particular interest arepyrido[2,3-b]pyrazines.

R⁸, which may be the same or different for the two CR⁸ values of W, X, Yand Z, is H, halo (for example bromo), C₁₋₄ alkyl (for example methyl),C₁₋₄ alkoxy (for example methoxy) or halo(C₁₋₄)alkyl (for exampletrifluoromethyl). Usually R⁸ will be H.

One of R and R², preferably R², is NR³R⁴. The other is typically halo,especially chloro or fluoro. In the case of pyrido[2,3-b]pyrazine ringsystems, the more active compounds are those where R² is NR³R⁴. R³ istypically C₁₋₈ alkyl (for example ethyl, n-propyl, n-butyl, sec-butyl(the S- or R-isomer or the racemate) and tert-butyl), halo(C₁₋₈)alkyl(for example 2,2,2-trifluoroethyl, 2,2,2-trifluoro-1-methylethyl (the S-or R-isomer or the racemate), 3,3,3-trifluoropropyl and4,4,4-trifluorobutyl), hydroxy(C₁₋₈)alkyl (for example hydroxyethyl),C₁₋₄ alkoxy(C₁₋₈)alkyl (for example methoxymethyl andmethoxy-iso-butyl), C₁₋₄ alkoxyhalo(C₁₋₈)alkyl (for example2-methoxy-2-trifluromethylethyl), tri-(C₁₋₄)alkylsilyl(C₁₋₆)alkyl (forexample trimethylsilylmethyl), C₁₋₄ alkylcarbonyl(C₁₋₈)alkyl (forexample 1-acetylethyl and 1-tert-butylcarbonylethyl), C₁₋₄alkylcarbonylhalo(C₁₋₈)alkyl (for example1-acetyl-2,2,2-trifluoroethyl), phenyl(₁₋₄)alkyl (for example benzyl),C₂₋₈ alkenyl (for example allyl and methylallyl), halo(C₂₋₈)alkenyl (forexample 3-methyl-4,4-difluorobut-3-enyl), C₂₋₈ alkynyl (for examplepropargyl), C₃₋₈ cycloalkyl (for example cyclopropyl, cyclobutyl,cyclopentyl and cyclohexyl) optionally substituted with chloro, fluoroor methyl, C₃₋₈ cycloalkyl(C₁₋₄)alkyl (for example cyclopropylmethyl,cyclobutylmethyl, cyclopentylmethyl and cyclohexylmethyl), phenylamino,piperidino or morpholino, the phenyl ring of phenylalkyl or phenylaminobeing optionally substituted with one, two or three substituentsselected from halo (typically fluoro, chloro or bromo), C₁₋₄ alkyl(typically methyl), halo(C₁₋₄)alkyl (typically trifluoromethyl), C₁₋₄alkoxy (typically methoxy) and halo(C₁₋₄)alkoxy (typicallytrifluoromethoxy). R⁴ is typically H, C₁₋₄ alkyl (for example ethyl andn-propyl), halo(C₁₋₄)alkyl (for example 2,2,2-trifluoroethyl) or amino.Alternatively R³ and R⁴ together form a C₄₋₆ alkylene chain optionallysubstituted with methyl, for example 3-methylpentylene, or, togetherwith the nitrogen atom to which they are attached, R³ and R⁴ form amorpholine, thiomorpholine, thiomorpholine S-oxide or thiomorpholineS-dioxide ring or a piperazine or piperazine N—(C₁₋₄)alkyl (especiallyN-methyl) ring, in which the morpholine or piperazine rings areoptionally substituted with methyl.

Typically R¹ is phenyl optionally substituted with from one to fivehalogen atoms, particularly fluorine and chlorine atoms and especiallyfluorine atoms or with from one to three substituents selected from halo(for example fluoro and chloro), C₁₋₄ alkyl (for example methyl),halo(C₁₋₄)alkyl (for example trifluoromethyl), C₁₋₄ alkoxy (for examplemethoxy) or halo(C₁₋₄)alkoxy (for example trifluoromethoxy). Examplesare 2,6-difluorophenyl, 2-fluoro-6-chlorophenyl, 2,5,6-trifluorophenyl,2,4,6-trifluorophenyl, 2,6-difluoro-4-methoxyphenyl, pentafluorophenyl,2-fluorophenyl, 2,3,5,6-tetrafluorophenyl, 2-chloro-4,6-difluorophenyl,2-chlorophenyl, 2,6-dichlorophenyl, 2,4-dichlorophenyl,2,4,6-trichlorophenyl, 2,3,6-tri-chlorophenyl, pentachlorophenyl,2-fluoro-4,6-dichlorophenyl, 4-fluoro-2,6-dichlorophenyl, 2-bromophenyl,2-fluoro-6-bromophenyl, 2-bromo-4,6-difluorophenyl,2-fluoro-6-methyl-phenyl, 2-chloro-6-methylphenyl, 2-methoxyphenyl,2,6-dimethoxyphenyl, 2-fluoro-6-methoxyphenyl, 2-trifluoromethylphenyl,2-fluoro-6-trifluoromethylphenyl, 2,6-di-(trifluoro-methyl)phenyl,2-chloro-6-trifluoromethylphenyl, 2,4-difluoro-6-trifluoromethylphenyl,2,4-difluoro-6-methoxyphenyl and 2,4-difluoro-6-methylphenyl.

Also of particular interest are compounds where R¹ is pyridyl optionallysubstituted with from one to four halogen atoms or with from one tothree substituents selected from halo (for example fluoro and chloro),C₁₋₄ alkyl (for example methyl), halo(C₁₋₄)alkyl (for exampletrifluoromethyl), C₁₋₄ alkoxy (for example methoxy) or halo(C₁₋₄)alkoxy(for example trifluoromethoxy). Examples are 2,4-difluoropyrid-3-yl,3,5-difluoropyrid-4-yl, tetrafluoropyrid-4-yl, 3-fluoropyrid-2-yl,4-fluoropyrid-3-yl, 3-fluoropyrid-4-yl, 2-fluoropyrid-3-yl,2,4,6-trifluoropyrid-3-yl, 3,5-difluoropyrid-2-yl,2,6-difluoropyrid-3-yl, 2,4-difluoro-6-methoxypyrid-3-yl,2-fluoro-4-chloropyrid-3-yl, 3-fluoro-5-chloropyrid-4-yl,2-chloro-4-fluoropyrid-3-yl, 2,4-dichloropyrid-3-yl, 3-chloropyrid-2-yl1,4-chloropyrid-3-yl, 3-chloropyrid-4-yl, 2-chloropyrid-3-yl,3-trifluoromethylpyrid-2-yl, 4-trifluoromethylpyrid-3-yl,3,5-dichloropyrid-2-yl, 4,6-dichloropyrid-3-yl,3-trifluoromethylpyrid-4-yl, 2-trifluoromethylpyrid-3-yl,2-fluoro-4-trifluoromethylpyrid-3-yl,3-fluoro-5-trifluoromethylpyrid-4-yl,4-fluoro-2-trifluoromethylpyrid-3-yl, 2,6-dichloropyrid-3-yl,3,5-dichloropyrid-4-yl, 3-chloro-6-trifluoromethylpyrid-2-yl,3-fluoro-6-trifluoromethylpyrid-2-yl, pyrid-2-yl, pyrid-3-yl andpyrid-4-yl.

Also of particular interest are compounds where R¹ is 2- or 3-thienyloptionally substituted with from one to three halogen atoms or with fromone to three substituents selected from halo (for example fluoro andchloro), C₁₋₄ alkyl (for example methyl), halo-(C₁₋₄)alkyl (for exampletrifluoromethyl), C₁₋₄ alkoxy (for example methoxy) or halo(C₁₋₄)alkoxy(for example trifluoromethoxy). Examples are 3-fluorothien-2-yl,3-chlorothien-2-yl, 2,4-difluorothien-3-yl, 2,4-dichlorothien-3-yl and2,4,5-trichlorothien-3-yl.

Examples of other values of R¹ of especial interest are unsubstitutedpiperidino and morpholino, 2-methylpiperidino, 2,6-dimethylpiperidinoand 2,6-dimethylmorpholino.

In one aspect the invention provides a compound of the general formula(1) wherein

W and X, W and Z, X and Y or Y and Z are N and the other two are CR⁸;

R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl;

one of R and R² (preferably R²) is NR³R⁴ and the other is halo;

R¹ is halo, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, C₃₋₈ cycloalkyl,C₃₋₈ cycloalkyl(C₁₋₆)alkyl, C₁₋₈ alkoxy, C₁₋₈ alkylthio, aryl, aryloxy,arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(C₁₋₄)alkyl,aryl(C₁₋₄)alkoxy, heteroaryl(C₁₋₄)alkyl, heteroaryl(C₁₋₄)alkoxy,aryl(C₁₋₄)-alkylthio, heteroaryl(C₁₋₄)alkylthio, morpholino, piperidinoor pyrrolidino;

R³ and R⁴ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl,aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl,heteroaryl, heteroaryl(C₁₋₈)alkyl, NR⁵R⁶, provided that not both R³ andR⁴ are H or NR⁵R⁶, or

R³ and R⁴ together form a C₃₋₇ alkylene or C₃₋₇ alkenylene chainoptionally substituted with one or more C₁₋₄ alkyl or C₁₋₄ alkoxygroups, or,

together with the nitrogen atom to which they are attached, R³ and R⁴form a morpholine, thiomorpholine, thiomorpholine S-oxide orthiomorpholine S-dioxide ring or a piperazine or piperazineN—(C₁₋₄)alkyl (especially N-methyl) ring; and

R⁵ and R⁶ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl,aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl,heteroaryl or heteroaryl(C₁₋₈)alkyl;

any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups ormoieties (other than for R⁸) being optionally substituted with halogen,cyano, C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxycarbonyl, C₁₋₆haloalkoxy, C₁₋₆ alkylthio, tri(C₁₋₄)alkylsilyl, C₁₋₆ alkylamino or C₁₋₆dialkylamino,

any of the foregoing morpholine, thiomorpholine, piperidine, piperazineand pyrrolidine rings being optionally substituted with C₁₋₄ alkyl(especially methyl), and

any of the foregoing aryl, heteroaryl, aryloxy or heteroaryl groupsbeing optionally substituted with one or more substituents selected fromhalo, hydroxy, mercapto, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆alkoxy, C₂₋₆ alkenyloxy, C₂₋₇₆ alkynyloxy, halo(C₁₋₆)alkyl,halo(C₁₋₆)alkoxy, C₁₋₆ alkylthio, halo(C₁₋₆)alkylthio,hydroxy(C₁₋₆)alkyl, C₁₋₄ alkoxy(C₁₋₆)-alkyl, C₃₋₆ cycloalkyl, C₃₋₆cycloalkyl(C₁₋₄)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano,thiocyanato, isothiocyanato, nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″,—CONR′″R″″, —SO₂R′″, —OSO₂R′″, —COR′″, —CR′″═NR″″ or —N═CR′″R″″, inwhich R′″ and R″″ are independently hydrogen, C₁₋₄ alkyl,halo(C₁₋₄)alkyl, C₁₋₄ alkoxy, halo(C₁₋₄)alkoxy, C₁₋₄ alkylthio, C₃₋₆cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenyl or benzyl, the phenyl andbenzyl groups being optionally substituted with halogen, C₁₋₄ alkyl orC₁₋₄ alkoxy. Of particular interest are compounds where W and Z are bothN and X and Y are both CH.

The invention includes a compound of the general formula (1) as definedimmediately above except that: C₇ alkylene and C₃₋₇ alkenylene areexcluded as chains formed by R³ and R⁴; the C₃₋₆ chain that R³ and R⁴may form may only be optionally substituted with one or more methylgroups; thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxideand piperazine are excluded as rings that R³ and R⁴ may form;tri(C₁₋₄)alkylsilyl is excluded as a substituent of any alkyl, alkenyl,alkynyl or cycloalkyl group or moiety, and any morpholine, piperidine orpyrrolidine ring is unsubstituted.

In another aspect the invention provides a compound of the generalformula (1) wherein

W and X, W and Z, X and Y or Y and Z are N and the other two are CR⁸;

R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl;

one of R and R² (preferably R²) is NR³R⁴ and the other is halo;

R¹ is halo, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, C₃₋₈ cycloalkyl,C₃₋₈ cycloalkyl(C₁₋₆)alkyl, C₁₋₈ alkoxy, C₁₋₈ alkylthio, aryl, aryloxy,arylthio, heteroaryl, heteroaryloxy, heteroarylthio, aryl(C₁₋₄)alkyl,aryl(C₁₋₄)alkoxy, heteroaryl(C₁₋₄)alkyl, heteroaryl(C₁₋₄)alkoxy,aryl(C₁₋₄)-alkylthio, heteroaryl(C₁₋₄)alkylthio, morpholino, piperidinoor pyrrolidino;

R³ is C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₂₋₄ alkenyl, C₃₋₆ cycloalkyl, C₃₋₆cycloalkyl(C₁₋₄)alkyl or phenylamino in which the phenyl ring isoptionally substituted with one, two or three substituents selected fromhalo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy and halo(C₁₋₄)alkoxy; and

R⁴ is H, C₁₋₄ alkyl or amino, or

R³ and R⁴ together form a C₄₋₆ alkylene chain optionally substitutedwith C₁₋₄ alkyl or C₁₋₄ alkoxy, or,

together with the nitrogen atom to which they are attached, R³ and R⁴form a morpholine, thiomorpholine, thiomorpholine S-oxide orthiomorpholine S-dioxide ring or a piperazine or piperazineN—(C₁₋₄)alkyl (especially N-methyl) ring;

any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups ormoieties (other than for R⁸) being optionally substituted with halogen,cyano, C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxycarbonyl, C₁₋₆haloalkoxy, C₁₋₆ alkylthio, tri(C₁₋₄)alkylsilyl, C₁₋₆ alkylamino or C₁₋₆dialkylamino,

any of the foregoing morpholine, thiomorpholine, piperidine, piperazineand pyrrolidine rings being optionally substituted with C₁₋₄ alkyl(especially methyl), and

any of the foregoing aryl or heteroaryl groups or moieties beingoptionally substituted with one or more substituents selected from halo,hydroxy, mercapto, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ alkoxy,C₂₋₄ alkenyloxy, C₂₋₆ alkynyloxy, halo(C₁₋₆)alkyl, halo(C₁₋₆)alkoxy,C₁₋₆ alkylthio, halo(C₁₋₆)alkylthio, hydroxy(C₁₋₆)alkyl, C₁₋₄alkoxy(C₁₋₆)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenoxy,benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato,nitro, —NR′″ R″″, —NHCOR′″, —NHCONR′″R″″, —CONR′″R″″, —SO₂R′″, —OSO₂R′″,—COR′″, —CR′″═NR″″ or —N═CR′″R″″, in which R′″ and R″″ are independentlyhydrogen, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy, halo(C₁₋₄)alkoxy,C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenyl orbenzyl, the phenyl and benzyl groups being optionally substituted withhalogen, C₁₋₄ alkyl or C₁₋₄ alkoxy.

Of particular interest are compounds where W and Z are both N and X andY are both CH.

The invention includes a compound of the general formula (1) as definedimmediately above except that: the C₄₋₆ chain that R³ and R⁴ may formmay only be optionally substituted with methyl; thiomorpholine,thiomorpholine S-oxide, thiomorpholine S-dioxide and piperazine areexcluded as rings that R³ and R⁴ may form; tri(C₁₋₄)alkylsilyl isexcluded as a substituent of any alkyl, alkenyl, alkynyl or cycloalkylgroup or moiety, and any morpholine, piperidine or pyrrolidine ring isunsubstituted.

In yet another aspect the invention provides a compound of the generalformula (1) wherein

W and X, W and Z, X and Y or Y and Z are N and the other two are CR⁸;

R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl;

R and R² are independently H, halo, C₁₋₈ alkyl, C₁₋₈ alkoxy, C₁₋₈alkylthio, C₂₋₈ alkenyl, C₂₋₈ alkynyl, cyano or NR³R⁴, provided that atleast one of R and R² (preferably R²) is N³R⁴;

R¹ is optionally substituted phenyl;

R³ and R⁴ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl,aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl,heteroaryl, heteroaryl(C₁₋₈)alkyl, NR⁵R⁶, provided that not both R³ andR⁴ are H or NR⁵R⁶, or

R³ and R⁴ together form a C₃₋₇ alkylene or C₃₋₇ alkenylene chainoptionally substituted with one or more C₁₋₄ alkyl or C₁₋₄ alkoxygroups, or,

together with the nitrogen atom to which they are attached, R³ and R⁴form a morpholine, thiomorpholine, thiomorpholine S-oxide orthiomorpholine S-dioxide ring or a piperazine or piperazineN—(C₁₋₄)alkyl (especially N-methyl) ring; and

R⁵ and R⁶ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl,aryl, aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl,heteroaryl or heteroaryl(C₁₋₈)alkyl;

any of the foregoing alkyl, alkenyl, alkynyl or cycloalkyl groups ormoieties (other than for R⁸) being optionally substituted with halogen,cyano, C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆ alkoxycarbonyl, C₁₋₆haloalkoxy, C₁₋₆ alkylthio, tri(C₁₋₄)alkylsilyl, C₁₋₆ alkylamino or C₁₋₆dialkylamino,

any of the foregoing morpholine, thiomorpholine, piperidine, piperazineand pyrrolidine rings being optionally substituted with C₁₋₄ alkyl(especially methyl), and

any of the foregoing aryl or heteroaryl groups or moieties, includingthe phenyl group of R¹, being optionally substituted with one or moresubstituents selected from halo, hydroxy, mercapto, C₁₋₆ alkyl, C₂₋₆alkenyl, C₂₋₆ alkynyl, C₁₋₆ alkoxy, C₂₋₆ alkenyloxy, C₂₋₆ alkynyloxy,halo(C₁₋₆)alkyl, halo(C₁₋₆)alkoxy, C₁₋₆ alkylthio, halo(C₁₋₆)alkylthio,hydroxy-(C₁₋₆)alkyl, C₁₋₄ alkoxy(C₁₋₆)alkyl, C₃₋₆ cycloalkyl, C₃₋₆cycloalkyl(C₁₋₄)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano,thiocyanato, isothiocyanato, nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″,—CON′″R″″, —SO₂R′″, —OSO₂R′″, —COR′″, —CR′″═NR″″ or —N═CR′″R″″, in whichR′″ and R″″ are independently hydrogen, C₁₋₄ alkyl, halo(C₁₋₄)alkyl,C₁₋₄ alkoxy, halo(C₁₋₄)alkoxy, C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆cycloalkyl(C₁₋₄)alkyl, phenyl or benzyl, the phenyl and benzyl groupsbeing optionally substituted with halogen, C₁₋₄ alkyl or C₁₋₄ alkoxy. Ofparticular interest are compounds where W and Z are both N and X and Yare both CH.

The invention includes a compound of the general formula (1) as definedimmediately above except that: C₁₋₈ alkoxy and C₁₋₈ alkylthio areexcluded as values of R and R²; C₇ alkylene and C₃₋₇ alkenylene areexcluded as chains formed by R³ and R⁴; the C₃₋₆ chain that R³ and R⁴may form may only be optionally substituted with one or more methylgroups; thiomorpholine, thiomorpholine S-oxide, thiomorpholine S-dioxideand piperazine are excluded as rings that R³ and R⁴ may form;tri(C₁₋₄)alkylsilyl is excluded as a substituent of any alkyl, alkenyl,alkynyl or cycloalkyl group or moiety, and the morpholine ring that R³and R⁴ may form is unsubstituted.

In still yet another aspect the invention provides a compound of thegeneral formula (1) wherein

W and X, W and Z, X and Y or Y and Z are N and the other two are CR⁸;

R⁸ is H, halo(e.g. fluoro, chloro or bromo), C₁₋₄ alkyl (e.g. methyl),C₁₋₄ alkoxy (e.g. methoxy) or halo(C₁₋₄)alkyl (e.g. trifluoromethyl);

R is H, halo (e.g. fluoro, chloro or bromo), C₁₋₄ alkyl (e.g. methyl),C₁₋₄ alkoxy (e.g. methoxy) or cyano;

R¹ is phenyl optionally substituted with from one to five halogen atomsor with from one to three substituents selected from halo, C₁₋₄ alkyl,halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkoxy, pyridyl optionallysubstituted with from one to four halogen atoms or with from one tothree substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄alkoxy or halo(C₁₋₄)alkoxy, 2- or 3-thienyl optionally substituted withfrom one to three halogen atoms or with from one to three substituentsselected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy orhalo(C₁₋₄)alkoxy, or piperidino or morpholino both optionallysubstituted with one or two methyl groups;

R² is NR³R⁴;

R³ is C₁₋₈ alkyl, halo(C₁₋₈)alkyl, hydroxy(C₁₋₈)alkyl, C₁₋₄alkoxy(C₁₋₈)alkyl, C₁₋₄ alkoxyhalo(C₁₋₈)alkyl,tri(C₁₋₄)alkylsilyl(C₁₋₆)alkyl, C₁₋₄ alkylcarbonyl(C₁₋₈)alkyl, C₁₋₄alkylcarbonylhalo(C₁₋₈)alkyl, phenyl(₁₋₄)alkyl, C₂₋₈ alkenyl,halo(C₂₋₈)alkenyl, C₂₋₈ alkynyl, C₃₋₈ cycloalkyl optionally substitutedwith chloro, fluoro or methyl, C₃₋₈ cycloalkyl(C₁₋₄)alkyl, phenylamino,piperidino or morpholino, the phenyl ring of phenylalkyl or phenylaminobeing optionally substituted with one, two or three substituentsselected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy andhalo(C₁₋₄)alkoxy; and

R⁴ is H, C₁₋₄ alkyl, halo(C₁₋₄)alkyl or amino, or

R³ and R⁴ together form a C₃₋₇ alkylene or C₃₋₇ alkenylene chainoptionally substituted with methyl, or,

together with the nitrogen atom to which they are attached, R³ and R⁴form a morpholine, thiomorpholine, thiomorpholine S-oxide orthiomorpholine S-dioxide ring or a piperazine or piperazineN—(C₁₋₄)alkyl (especially N-methyl) ring, in which the morpholine orpiperazine rings are optionally substituted with methyl.

Of particular interest are compounds where W and Z are both N and X andY are both CH.

In still yet another aspect the invention provides a compound of thegeneral formula (1) wherein

W and X, W and Z, X and Y or Y and Z are N and the other two are CR⁸;

R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl;

R is halo;

R¹ is phenyl optionally substituted with from one to five halogen atomsor with from one to three substituents selected from halo, C₁₋₄ alkyl,halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)-alkoxy;

R² is NR³R⁴;

R³ is C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₂₋₄ alkenyl, C₃₋₆ cycloalkyl, C₃₋₆cycloalkyl(C₁₋₄)alkyl or phenylamino in which the phenyl ring isoptionally substituted with one, two or three substituents selected fromhalo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy and halo(C₁₋₄)alkoxy; and

R⁴ is H, C₁₋₄ alkyl or amino, or R³ and R⁴ together form a C₄₋₆ alkylenechain optionally substituted with methyl, or, together with the nitrogenatom to which they are attached, R³ and R⁴ form a morpholine ring.

Of particular interest are compounds where W and Z are both N and X andY are both CH.

Compounds that form part of the invention are illustrated in Tables 1 to127 below. Characterising data are given later in the Examples and inTable 133.

In Table 1 the compounds have the general formula (1A), where W and Zare N, X and Y are CH, R is Cl, R¹ is 2,4,6-trifluorophenyl and R³ andR⁴ are as shown in the table. TABLE 1 (1A)

Cmpd No R³ R⁴  1 C₂H₅ H  2 n-C₃H₇ H  3 i-C₃H₇ H  4 n-C₄H₉ H  5 t-C₄H₉ H 6 CH₂═CHCH₂ H  7 CH₂═C(CH₃)CH₂ H  8 CF₃CH₂ H  9 CF₃CH₂CH₂ H  10CF₃CH₂CH₂CH₂ H  11 CF₃(CH₃)CH H  12 (S)-CF₃(CH₃)CH H  13 (R)-CF₃(CH₃)CHH  14 cyclo-C₃H₅ H  15 cyclo-C₄H₇ H  16 cyclo-C₅H₉ H  17 cyclo-C₆H₁₁ H 18 cyclo-C₃H₅CH₂ H  19 cyclo-C₄H₇CH₂ H  20 —(CH₂)₂O(CH₂)₂—  21cyclo-C₆H₁₁CH₂ H  22 —(CH₂)₂CH(CH₃)(CH₂)₂—  23 CH₃CH₂(CH₃)CH H  24(S)-CH₃CH₂(CH₃)CH H  25 (R)-CH₃CH₂(CH₃)CH H  26 C₂H₅ C₂H₅  27 n-C₃H₇n-C₃H₇  28 CH₂═C(CH₃)CH₂ C₂H₅  29 CF₃CH₂ C₂H₅  30 C₂H₅ NH₂  31 n-C₃H₇NH₂  32 i-C₃H₇ NH₂  33 n-C₄H₉ NH₂  34 CH₂═CHCH₂ NH₂  35 CH₂═C(CH₃)CH₂NH₂  36 CF₂═CFCH₂CH₂ NH₂  37 CF₃CH₂ NH₂  38 CF₃CH₂CH₂ NH₂  39CF₃CH₂CH₂CH₂ NH₂  40 4-t-C₄H₉—C₆H₄NH H  41 4-F—C₆H₄NH H  42 C₆H₅NH H  434-CH₃—C₆H₄NH H  44 4-Br—C₆H₄NH H  45 2-F—C₆H₄NH H  46 3,4-Cl₂—C₆H₃NH H 47 3-CF₃—C₆H₄NH H  48 3,5-Cl₂—C₆H₃NH H  49 4-CF₃O—C₆H₅NH H  502-CF₃—C₆H₄NH H  51 4-CF₃—C₆H₄NH H  52 2-Br—C₆H₄NH H  53 2-Cl—C₆H₄NH H 54 2-CH₃-4-Cl—C₆H₃NH H  55 2-CH₃-5-F—C₆H₃NH H  56 3-Cl—C₆H₄NH H  57 CH₃H  58 (CH₃)₂CHCH₂ H  59 (CH₃)₃CCH₂ H  60 (CH₃)₃C(CH₃)CH H  61CH₃CH₂(CH₃)₂C H  62 CH₃CH₂(CF₃)CH H  63 (S)-CH₃CH₂(CF₃)CH H  64(R)-CH₃CH₂(CF₃)CH H  65 CH₃CH₂(CH₃CH₂)CH H  66 (CH₃)₂CH(CH₃CH₂)CH H  67(CH₃)₂CH(CH₃)CH H  68 (CH₃)₂CH(CF₃)CH H  69 (S)-(CH₃)₂CH(CF₃)CH H  70(R)-(CH₃)₂CH(CF₃)CH H  71 HC═C(CH₃)CH₂ H  72 CH₂═CH(CH₃CH₂)CH H  73CH₃CH₂CH₂(CH₃)CH H  74 CH₃CH₂CH₂(CF₃)CH H  75 (S)-CH₃CH₂CH₂(CF₃)CH H  76(R)-CH₃CH₂CH₂(CF₃)CH H  77 CH₃CH₂CH₂(CH₃)₂C H  78 CH₃CH₂(CH₃)CHCH₂ H  79(CH₃)₂CHCH₂CH₂ H  80 (CH₃)₃CCH₂CH₂ H  81 CH₃CH₂(CH₃)CH(CH₃)CH H  82CH₃CH₂(CH₃)CH(CF₃)CH H  83 (S)-CH₃CH₂(CH₃)CH(CF₃)CH H  84(R)-CH₃CH₂(CH₃)CH(CF₃)CH H  85 CH₃(CH₃)CHCH₂(CH₃)CH H  86CH₃(CH₃)CHCH₂(CF₃)CH H  87 (S)-CH₃(CH₃)CHCH₂(CF₃)CH H  88(R)-CH₃(CH₃)CHCH₂(CF₃)CH H  89 (CH₃)₂CH(CH₃)CH(CH₃)CH₂ H  90(CH₃)₃CCH₂(CH₃)CH H  91 E-CH₃CH═CH(CH₃)CH H  92 E-CH₃CH═CH(CH₃CH₂)CH H 93 CH₃CH₂CH₂(CH₃CH₂)CH H  94 CH₃CH₂(CH₃CH₂)CHCH₂ H  95 CF₂═CFCH₂CH₂ H 96 CF₃CH₂(CH₃)CHCH₂ H  97 CF₃CF₂CH₂CH₂ H  98 CF₃CF₂CF₂CH₂ H  99CF₂═C(CH₃)CH₂CH₂ H 100 CH₃CH₂CH₂CH₂CH₂ H 101 CH₃CH₂CH₂CH₂(CH₃)CH H 102CH₃CH₂CH₂(CH₃)CHCH₂ H 103 CH₃CH₂(CH₃)CHCH₂CH₂ H 104CH₃CH₂CH₂(CH₃)CH(CH₃)CH H 105 CH₃CH₂(CH₃)CHCH₂(CH₃)CH H 106 HOCH₂CH₂ H107 CH₃OCH₂CH₂ H 108 CH₃OCH₂(CH₃)CH H 109 CH₃OCH₂(CF₃)CH H 110CH₃OCH₂(CH₃)₂C H 111 CH₃O(CH₃)CHCH₂ H 112 CH₃O(CH₃)CH(CH₃)CH H 113HC≡CCH₂ H 114 CH₃C≡CCH₂ H 115 HC≡CCH₂CH₂ H 116 HOCH₂CH₂CH₂ H 117CH₃OCH₂CH₂CH₂ H 118 (CH₃)₃SiCH₂ H 119 C₆H₅CH₂ H 120 C₆H₅(CH₃)CH H 1214-F—C₆H₄CH₂ H 122 4-Cl—C₆H₄CH₂ H 123 4-F—C₆H₅(CH₃)CH H 1244-Cl—C₆H₅(CH₃)CH H 125 C₆H₅CH₂CH₂ H 126 4-F—C₆H₅CH₂CH₂ H 1271-piperidino H 128 1-pyrrolidino H 129 cyclo-C₅H₉CH₂ H 130Bicyclo[2.2.1]hept-2-yl H 131 1-CH₃-cyclopropyl H 132cis-2-CH₃-cyclopropyl H 133 trans-2-CH₃-cyclopropyl H 1342,2-(CH₃)₂-cyclopropyl H 135 1-CH₃-cyclobutyl H 136 cis-2-CH₃-cyclobutylH 137 trans-2-CH₃-cyclobutyl H 138 cis-3-CH₃-cyclobutyl H 139trans-3-CH₃-cyclobutyl H 140 2,2-(CH₃)₂-cyclobutyl H 1413,3-(CH₃)₂-cyclobutyl H 142 1-CH₃-cyclopentyl H 143cis-2-CH₃-cyclopentyl H 144 trans-2-CH₃-cyclopentyl H 145cis-3-CH₃-cyclopentyl H 146 trans-3-CH₃-cyclopentyl H 1472,2-(CH₃)₂-cyclopentyl H 148 3,3-(CH₃)₂-cyclopentyl H 1491-CH₃-cyclohexyl H 150 cis-2-CH₃-cyclohexyl H 151 trans-2-CH₃-cyclohexylH 152 cis-3-CH₃-cyclohexyl H 153 trans-3-CH₃-cyclohexyl H 1542,2-(CH₃)₂-cyclohexyl H 155 3,3-(CH₃)₂-cyclohexyl H 156cis-4-CH₃-cyclohexyl H 157 trans-4-CH₃-cyclohexyl H 1584,4-(CH₃)₂-cyclohexyl H 159 4-(CH₃)₃C-cyclohexyl H 160 —(CH₂)₃— 161—(CH₂)₄— 162 —(CH₂)₅— 163 —(CH₂)₆— 164 —(CH₂)₂(CH₃)₂C(CH₂)₂— 165—(CH₃)CH(CH₂)₂— 166 —(CH₃)CH(CH₂)₃— 167 —(CH₃)CH(CH₂)₄— 168—(CH₃)CH(CH₂)₅— 169 —CH₂CH═CH(CH₂)₂— 170 —(CH₂)₂NH(CH₂)₂— 171—(CH₂)₂NCH₃(CH₂)₂— 172 —(CH₂)₂S(CH₂)₂— 173 —(CH₂)₂SO(CH₂)₂— 174—(CH₂)₂SO₂(CH₂)₂— 175 —CH₂(CH₃)CHO(CH₃)CHCH₂— 176 C₂H₅ CH₃ 177 n-C₃H₇CH₃ 178 i-C₃H₇ CH₃ 179 n-C₄H₉ CH₃ 180 t-C₄H₉ CH₃ 181 CH₂═CHCH₂ CH₃ 182CH₂═C(CH₃)CH₂ CH₃ 183 CF₃CH₂ CH₃ 184 CF₃CH₂CH₂ CH₃ 185 CF₃CH₂CH₂CH₂ CH₃186 CF₃(CH₃)CH CH₃ 187 (S)-CF₃(CH₃)CH CH₃ 188 (R)-CF₃(CH₃)CH CH₃ 189cyclo-C₃H₅ CH₃ 190 cyclo-C₄H₇ CH₃ 191 cyclo-C₅H₉ CH₃ 192 cyclo-C₆H₁₁ CH₃193 cyclo-C₃H₅CH₂ CH₃ 194 cyclo-C₄H₇CH₂ CH₃ 195 cyclo-C₆H₁₁CH₂ CH₃ 196CH₃CH₂(CH₃)CH CH₃ 197 (S)-CH₃CH₂(CH₃)CH CH₃ 198 (R)-CH₃CH₂(CH₃)CH CH₃199 cyclo-C₇H₁₃ CH₃ 200 CH₂═C(CH₃)CH₂ C₂H₅ 201 CF₃CH₂ C₂H₅ 2024-t-C₄H₉—C₆H₄NH CH₃ 203 4-F—C₆H₄NH CH₃ 204 C₆H₅NH CH₃ 205 4-CH₃—C₆H₄NHCH₃ 206 4-Br—C₆H₄NH CH₃ 207 2-F—C₆H₄NH CH₃ 208 3,4-Cl₂—C₆H₃NH CH₃ 2093-CF₃—C₆H₄NH CH₃ 210 3,5-Cl₂—C₆H₃NH CH₃ 211 4-CF₃O—C₆H₅NH CH₃ 2122-CF₃—C₆H₄NH CH₃ 213 4-CF₃—C₆H₄NH CH₃ 214 2-Br—C₆H₄NH CH₃ 2152-Cl—C₆H₄NH CH₃ 216 2-CH₃-4-Cl—C₆H₃NH CH₃ 217 2-CH₃-5-F—C₆H₃NH CH₃ 2183-Cl—C₆H₄NH CH₃ 219 CH₃ CH₃ 220 (CH₃)₂CHCH₂ CH₃ 221 (CH₃)₃CCH₂ CH₃ 222(CH₃)₃C(CH₃)CH CH₃ 223 CH₃CH₂(CH₃)₂C CH₃ 224 CH₃CH₂(CF₃)CH CH₃ 225(S)-CH₃CH₂(CF₃)CH CH₃ 226 (R)-CH₃CH₂(CF₃)CH CH₃ 227 CH₃CH₂(CH₃CH₂)CH CH₃228 (CH₃)₂CH(CH₃CH₂)CH CH₃ 229 (CH₃)₂CH(CH₃)CH CH₃ 230 (CH₃)₂CH(CF₃)CHCH₃ 231 (S)-(CH₃)₂CH(CF₃)CH CH₃ 232 (R)-(CH₃)₂CH(CF₃)CH CH₃ 233HC═C(CH₃)CH₂ CH₃ 234 CH₂═CH(CH₃CH₂)CH CH₃ 235 CH₃CH₂CH₂(CH₃)CH CH₃ 236CH₃CH₂CH₂(CF₃)CH CH₃ 237 (S)-CH₃CH₂CH₂(CF₃)CH CH₃ 238(R)-CH₃CH₂CH₂(CF₃)CH CH₃ 239 CH₃CH₂CH₂(CH₃)₂C CH₃ 240 CH₃CH₂(CH₃)CHCH₂CH₃ 241 (CH₃)₂CHCH₂CH₂ CH₃ 242 (CH₃)₃CCH₂CH₂ CH₃ 243CH₃CH₂(CH₃)CH(CH₃)CH CH₃ 244 CH₃CH₂(CH₃)CH(CF₃)CH CH₃ 245(S)-CH₃CH₂(CH₃)CH(CF₃)CH CH₃ 246 (R)-CH₃CH₂(CH₃)CH(CF₃)CH CH₃ 247CH₃(CH₃)CHCH₂(CH₃)CH CH₃ 248 CH₃(CH₃)CHCH₂(CF₃)CH CH₃ 249(S)-CH₃(CH₃)CHCH₂(CF₃)CH CH₃ 250 (R)-CH₃(CH₃)CHCH₂(CF₃)CH CH₃ 251(CH₃)₂CH(CH₃)CH(CH₃)CH₂ CH₃ 252 (CH₃)₃CCH₂(CH₃)CH CH₃ 253E-CH₃CH═CH(CH₃)CH CH₃ 254 E-CH₃CH═CH(CH₃CH₂)CH CH₃ 255CH₃CH₂CH₂(CH₃CH₂)CH CH₃ 256 CH₃CH₂(CH₃CH₂)CHCH₂ CH₃ 257 CF₂═CFCH₂CH₂ CH₃258 CF₃CH₂(CH₃)CHCH₂ CH₃ 259 CF₃CF₂CH₂CH₂ CH₃ 260 CF₃CF₂CF₂CH₂ CH₃ 261CF₂═C(CH₃)CH₂CH₂ CH₃ 262 CH₃CH₂CH₂CH₂CH₂ CH₃ 263 CH₃CH₂CH₂CH₂(CH₃)CH CH₃264 CH₃CH₂CH₂(CH₃)CHCH₂ CH₃ 265 CH₃CH₂(CH₃)CHCH₂CH₂ CH₃ 266CH₃CH₂CH₂(CH₃)CH(CH₃)CH CH₃ 267 CH₃CH₂(CH₃)CHCH₂(CH₃)CH CH₃ 268 HOCH₂CH₂CH₃ 269 CH₃OCH₂CH₂ CH₃ 270 CH₃OCH₂(CH₃)CH CH₃ 271 CH₃OCH₂(CF₃)CH CH₃ 272CH₃OCH₂(CH₃)₂C CH₃ 273 CH₃O(CH₃)CHCH₂ CH₃ 274 CH₃O(CH₃)CH(CH₃)CH CH₃ 275HC≡CCH₂ CH₃ 276 CH₃C≡CCH₂ CH₃ 277 HC≡CCH₂CH₂ CH₃ 278 HOCH₂CH₂CH₂ CH₃ 279CH₃OCH₂CH₂CH₂ CH₃ 280 (CH₃)₃SiCH₂ CH₃ 281 C₆H₅CH₂ CH₃ 282 C₆H₅(CH₃)CHCH₃ 283 4-F—C₆H₄CH₂ CH₃ 284 4-Cl—C₆H₄CH₂ CH₃ 285 4-F—C₆H₅(CH₃)CH CH₃ 2864-Cl—C₆H₅(CH₃)CH CH₃ 287 C₆H₅CH₂CH₂ CH₃ 288 4-F—C₆H₅CH₂CH₂ CH₃ 2891-piperidino CH₃ 290 1-pyrrolidino CH₃ 291 cyclo-C₅H₉CH₂ CH₃ 292bicyclo[2.2.1]hept-2-yl CH₃ 293 1-CH₃-cyclopropyl CH₃ 294cis-2-CH₃-cyclopropyl CH₃ 295 trans-2-CH₃-cyclopropyl CH₃ 2962,2-(CH₃)₂-cyclopropyl CH₃ 297 1-CH₃-cyclobutyl CH₃ 298cis-2-CH₃-cyclobutyl CH₃ 299 trans-2-CH₃-cyclobutyl CH₃ 300cis-3-CH₃-cyclobutyl CH₃ 301 trans-3-CH₃-cyclobutyl CH₃ 3022,2-(CH₃)₂-cyclobutyl CH₃ 303 3,3-(CH₃)₂-cyclobutyl CH₃ 3041-CH₃-cyclopentyl CH₃ 305 cis-2-CH₃-cyclopentyl CH₃ 306trans-2-CH₃-cyclopentyl CH₃ 307 cis-3-CH₃-cyclopentyl CH₃ 308trans-3-CH₃-cyclopentyl CH₃ 309 2,2-(CH₃)₂-cyclopentyl CH₃ 3103,3-(CH₃)₂-cyclopentyl CH₃ 311 1-CH₃-cyclohexyl CH₃ 312cis-2-CH₃-cyclohexyl CH₃ 313 trans-2-CH₃-cyclohexyl CH₃ 314cis-3-CH₃-cyclohexyl CH₃ 315 trans-3-CH₃-cyclohexyl CH₃ 3162,2-(CH₃)₂-cyclohexyl CH₃ 317 3,3-(CH₃)₂-cyclohexyl CH₃ 318cis-4-CH₃-cyclohexyl CH₃ 319 trans-4-CH₃-cyclohexyl CH₃ 3204,4-(CH₃)₂-cyclohexyl CH₃ 321 4-(CH₃)₃C-cyclohexyl CH₃ 322 n-C₃H₇ C₂H₅323 i-C₃H₇ C₂H₅ 324 n-C₄H₉ C₂H₅ 325 t-C₄H₉ C₂H₅ 326 CH₂═CHCH₂ C₂H₅ 327CF₃CH₂CH₂ C₂H₅ 328 CF₃CH₂CH₂CH₂ C₂H₅ 329 CF₃(CH₃)CH C₂H₅ 330(S)-CF₃(CH₃)CH C₂H₅ 331 (R)-CF₃(CH₃)CH C₂H₅ 332 cyclo-C₃H₅ C₂H₅ 333cyclo-C₄H₇ C₂H₅ 334 cyclo-C₅H₉ C₂H₅ 335 cyclo-C₆H₁₁ C₂H₅ 336cyclo-C₃H₅CH₂ C₂H₅ 337 cyclo-C₄H₇CH₂ C₂H₅ 338 cyclo-C₆H₁₁CH₂ C₂H₅ 339CH₃CH₂(CH₃)CH C₂H₅ 340 (S)-CH₃CH₂(CH₃)CH C₂H₅ 341 (R)-CH₃CH₂(CH₃)CH C₂H₅342 cyclo-C₇H₁₃ C₂H₅ 343 4-t-C₄H₉—C₆H₄NH C₂H₅ 344 4-F—C₆H₄NH C₂H₅ 345C₆H₅NH C₂H₅ 346 4-CH₃—C₆H₄NH C₂H₅ 347 4-Br—C₆H₄NH C₂H₅ 348 2-F—C₆H₄NHC₂H₅ 349 3,4-Cl₂—C₆H₃NH C₂H₅ 350 3-CF₃—C₆H₄NH C₂H₅ 351 3,5-Cl₂—C₆H₃NHC₂H₅ 352 4-CF₃O—C₆H₅NH C₂H₅ 353 2-CF₃—C₆H₄NH C₂H₅ 354 4-CF₃—C₆H₄NH C₂H₅355 2-Br—C₆H₄NH C₂H₅ 356 2-Cl—C₆H₄NH C₂H₅ 357 2-CH₃-4-Cl—C₆H₃NH C₂H₅ 3582-CH₃-5-F—C₆H₃NH C₂H₅ 359 3-Cl—C₆H₄NH C₂H₅ 360 (CH₃)₂CHCH₂ C₂H₅ 361(CH₃)₃CCH₂ C₂H₅ 362 (CH₃)₃C(CH₃)CH C₂H₅ 363 CH₃CH₂(CH₃)₂C C₂H₅ 364CH₃CH₂(CF₃)CH C₂H₅ 365 (S)-CH₃CH₂(CF₃)CH C₂H₅ 366 (R)-CH₃CH₂(CF₃)CH C₂H₅367 CH₃CH₂(CH₃CH₂)CH C₂H₅ 368 (CH₃)₂CH(CH₃CH₂)CH C₂H₅ 369(CH₃)₂CH(CH₃)CH C₂H₅ 370 (CH₃)₂CH(CF₃)CH C₂H₅ 371 (S)-(CH₃)₂CH(CF₃)CHC₂H₅ 372 (R)-(CH₃)₂CH(CF₃)CH C₂H₅ 373 HC═C(CH₃)CH₂ C₂H₅ 374CH₂═CH(CH₃CH₂)CH C₂H₅ 375 CH₃CH₂CH₂(CH₃)CH C₂H₅ 376 CH₃CH₂CH₂(CF₃)CHC₂H₅ 377 (S)-CH₃CH₂CH₂(CF₃)CH C₂H₅ 378 (R)-CH₃CH₂CH₂(CF₃)CH C₂H₅ 379CH₃CH₂CH₂(CH₃)₂C C₂H₅ 380 CH₃CH₂(CH₃)CHCH₂ C₂H₅ 381 (CH₃)₂CHCH₂CH₂ C₂H₅382 (CH₃)₃CCH₂CH₂ C₂H₅ 383 CH₃CH₂(CH₃)CH(CH₃)CH C₂H₅ 384CH₃CH₂(CH₃)CH(CF₃)CH C₂H₅ 385 (S)-CH₃CH₂(CH₃)CH(CF₃)CH C₂H₅ 386(R)-CH₃CH₂(CH₃)CH(CF₃)CH C₂H₅ 387 CH₃(CH₃)CHCH₂(CH₃)CH C₂H₅ 388CH₃(CH₃)CHCH₂(CF₃)CH C₂H₅ 389 (S)-CH₃(CH₃)CHCH₂(CF₃)CH C₂H₅ 390(R)-CH₃(CH₃)CHCH₂(CF₃)CH C₂H₅ 391 (CH₃)₂CH(CH₃)CH(CH₃)CH₂ C₂H₅ 392(CH₃)₃CCH₂(CH₃)CH C₂H₅ 393 E-CH₃CH═CH(CH₃)CH C₂H₅ 394E-CH₃CH═CH(CH₃CH₂)CH C₂H₅ 395 CH₃CH₂CH₂(CH₃CH₂)CH C₂H₅ 396CH₃CH₂(CH₃CH₂)CHCH₂ C₂H₅ 397 CF₂═CFCH₂CH₂ C₂H₅ 398 CF₃CH₂(CH₃)CHCH₂ C₂H₅399 CF₃CF₂CH₂CH₂ C₂H₅ 400 CF₃CF₂CF₂CH₂ C₂H₅ 401 CF₂═C(CH₃)CH₂CH₂ C₂H₅402 CH₃CH₂CH₂CH₂CH₂ C₂H₅ 403 CH₃CH₂CH₂CH₂(CH₃)CH C₂H₅ 404CH₃CH₂CH₂(CH₃)CHCH₂ C₂H₅ 405 CH₃CH₂(CH₃)CHCH₂CH₂ C₂H₅ 406CH₃CH₂CH₂(CH₃)CH(CH₃)CH C₂H₅ 407 CH₃CH₂(CH₃)CHCH₂(CH₃)CH C₂H₅ 408HOCH₂CH₂ C₂H₅ 409 CH₃OCH₂CH₂ C₂H₅ 410 CH₃OCH₂(CH₃)CH C₂H₅ 411CH₃OCH₂(CF₃)CH C₂H₅ 412 CH₃OCH₂(CH₃)₂C C₂H₅ 413 CH₃O(CH₃)CHCH₂ C₂H₅ 414CH₃O(CH₃)CH(CH₃)CH C₂H₅ 415 HC≡CCH₂ C₂H₅ 416 CH₃C≡CCH₂ C₂H₅ 417HC≡CCH₂CH₂ C₂H₅ 418 HOCH₂CH₂CH₂ C₂H₅ 419 CH₃OCH₂CH₂CH₂ C₂H₅ 420(CH₃)₃SiCH₂ C₂H₅ 421 C₆H₅CH₂ C₂H₅ 422 C₆H₅(CH₃)CH C₂H₅ 423 4-F—C₆H₄CH₂C₂H₅ 424 4-Cl—C₆H₄CH₂ C₂H₅ 425 4-F—C₆H₅(CH₃)CH C₂H₅ 426 4-Cl—C₆H₅(CH₃)CHC₂H₅ 427 C₆H₅CH₂CH₂ C₂H₅ 428 4-F—C₆H₅CH₂CH₂ C₂H₅ 429 1-piperidino C₂H₅430 1-pyrrolidino C₂H₅ 431 cyclo-C₅H₉CH₂ C₂H₅ 432Bicyclo[2.2.1]hept-2-yl C₂H₅ 433 1-CH₃-cyclopropyl C₂H₅ 434cis-2-CH₃-cyclopropyl C₂H₅ 435 trans-2-CH₃-cyclopropyl C₂H₅ 4362,2-(CH₃)₂-cyclopropyl C₂H₅ 437 1-CH₃-cyclobutyl C₂H₅ 438cis-2-CH₃-cyclobutyl C₂H₅ 439 trans-2-CH₃-cyclobutyl C₂H₅ 440cis-3-CH₃-cyclobutyl C₂H₅ 441 trans-3-CH₃-cyclobutyl C₂H₅ 4422,2-(CH₃)₂-cyclobutyl C₂H₅ 443 3,3-(CH₃)₂-cyclobutyl C₂H₅ 4441-CH₃-cyclopentyl C₂H₅ 445 cis-2-CH₃-cyclopentyl C₂H₅ 446trans-2-CH₃-cyclopentyl C₂H₅ 447 cis-3-CH₃-cyclopentyl C₂H₅ 448trans-3-CH₃-cyclopentyl C₂H₅ 449 2,2-(CH₃)₂-cyclopentyl C₂H₅ 4503,3-(CH₃)₂-cyclopentyl C₂H₅ 451 1-CH₃-cyclohexyl C₂H₅ 452cis-2-CH₃-cyclohexyl C₂H₅ 453 trans-2-CH₃-cyclohexyl C₂H₅ 454cis-3-CH₃-cyclohexyl C₂H₅ 355 trans-3-CH₃-cyclohexyl C₂H₅ 4562,2-(CH₃)₂-cyclohexyl C₂H₅ 457 3,3-(CH₃)₂-cyclohexyl C₂H₅ 458cis-4-CH₃-cyclohexyl C₂H₅ 459 trans-4-CH₃-cyclohexyl C₂H₅ 4604,4-(CH₃)₂-cyclohexyl C₂H₅ 461 4-(CH₃)₃C-cyclohexyl C₂H₅ 462 n-C₃H₇CF₃CH₂ 463 i-C₃H₇ CF₃CH₂ 464 n-C₄H₉ CF₃CH₂ 465 t-C₄H₉ CF₃CH₂ 466CH₂═CHCH₂ CF₃CH₂ 467 CH₂═C(CH₃)CH₂ CF₃CH₂ 468 CF₃CH₂ CF₃CH₂ 469CF₃CH₂CH₂ CF₃CH₂ 470 CF₃CH₂CH₂CH₂ CF₃CH₂ 471 CF₃(CH₃)CH CF₃CH₂ 472(S)-CF₃(CH₃)CH CF₃CH₂ 473 (R)-CF₃(CH₃)CH CF₃CH₂ 474 cyclo-C₃H₅ CF₃CH₂475 cyclo-C₄H₇ CF₃CH₂ 476 cyclo-C₅H₉ CF₃CH₂ 477 cyclo-C₆H₁₁ CF₃CH₂ 478cyclo-C₃H₅CH₂ CF₃CH₂ 479 cyclo-C₄H₇CH₂ CF₃CH₂ 480 cyclo-C₆H₁₁CH₂ CF₃CH₂481 CH₃CH₂(CH₃)CH CF₃CH₂ 482 (S)-CH₃CH₂(CH₃)CH CF₃CH₂ 483(R)-CH₃CH₂(CH₃)CH CF₃CH₂ 484 cyclo-C₇H₁₃ CF₃CH₂ 485 CH₂═C(CH₃)CH₂ CF₃CH₂486 CF₃CH₂ CF₃CH₂ 487 4-t-C₄H₉—C₆H₄NH CF₃CH₂ 488 4-F—C₆H₄NH CF₃CH₂ 489C₆H₅NH CF₃CH₂ 490 4-CH₃—C₆H₄NH CF₃CH₂ 491 4-Br—C₆H₄NH CF₃CH₂ 4922-F—C₆H₄NH CF₃CH₂ 493 3,4-Cl₂—C₆H₃NH CF₃CH₂ 494 3-CF₃—C₆H₄NH CF₃CH₂ 4953,5-Cl₂—C₆H₃NH CF₃CH₂ 496 4-CF₃O—C₆H₅NH CF₃CH₂ 497 2-CF₃—C₆H₄NH CF₃CH₂498 4-CF₃—C₆H₄NH CF₃CH₂ 499 2-Br—C₆H₄NH CF₃CH₂ 500 2-Cl—C₆H₄NH CF₃CH₂501 2-CH₃-4-Cl—C₆H₃NH CF₃CH₂ 502 2-CH₃-5-F—C₆H₃NH CF₃CH₂ 503 3-Cl—C₆H₄NHCF₃CH₂ 504 (CH₃)₂CHCH₂ CF₃CH₂ 505 (CH₃)₃CCH₂ CF₃CH₂ 506 (CH₃)₃C(CH₃)CHCF₃CH₂ 507 CH₃CH₂(CH₃)₂C CF₃CH₂ 508 CH₃CH₂(CF₃)CH CF₃CH₂ 509(S)-CH₃CH₂(CF₃)CH CF₃CH₂ 510 (R)-CH₃CH₂(CF₃)CH CF₃CH₂ 511CH₃CH₂(CH₃CH₂)CH CF₃CH₂ 512 (CH₃)₂CH(CH₃CH₂)CH CF₃CH₂ 513(CH₃)₂CH(CH₃)CH CF₃CH₂ 514 (CH₃)₂CH(CF₃)CH CF₃CH₂ 515(S)-(CH₃)₂CH(CF₃)CH CF₃CH₂ 516 (R)-(CH₃)₂CH(CF₃)CH CF₃CH₂ 517HC═C(CH₃)CH₂ CF₃CH₂ 518 CH₂═CH(CH₃CH₂)CH CF₃CH₂ 520 CH₃CH₂CH₂(CH₃)CHCF₃CH₂ 521 CH₃CH₂CH₂(CF₃)CH CF₃CH₂ 522 (S)-CH₃CH₂CH₂(CF₃)CH CF₃CH₂ 523(R)-CH₃CH₂CH₂(CF₃)CH CF₃CH₂ 524 CH₃CH₂CH₂(CH₃)₂C CF₃CH₂ 525CH₃CH₂(CH₃)CHCH₂ CF₃CH₂ 526 (CH₃)₂CHCH₂CH₂ CF₃CH₂ 527 (CH₃)₃CCH₂CH₂CF₃CH₂ 528 CH₃CH₂(CH₃)CH(CH₃)CH CF₃CH₂ 529 CH₃CH₂(CH₃)CH(CF₃)CH CF₃CH₂530 (S)-CH₃CH₂(CH₃)CH(CF₃)CH CF₃CH₂ 531 (R)-CH₃CH₂(CH₃)CH(CF₃)CH CF₃CH₂532 CH₃(CH₃)CHCH₂(CH₃)CH CF₃CH₂ 533 CH₃(CH₃)CHCH₂(CF₃)CH CF₃CH₂ 534(S)-CH₃(CH₃)CHCH₂(CF₃)CH CF₃CH₂ 535 (R)-CH₃(CH₃)CHCH₂(CF₃)CH CF₃CH₂ 536(CH₃)₂CH(CH₃)CH(CH₃)CH₂ CF₃CH₂ 537 (CH₃)₃CCH₂(CH₃)CH CF₃CH₂ 538E-CH₃CH═CH(CH₃)CH CF₃CH₂ 539 E-CH₃CH═CH(CH₃CH₂)CH CF₃CH₂ 540CH₃CH₂CH₂(CH₃CH₂)CH CF₃CH₂ 541 CH₃CH₂(CH₃CH₂)CHCH₂ CF₃CH₂ 542CF₂═CFCH₂CH₂ CF₃CH₂ 543 CF₃CH₂(CH₃)CHCH₂ CF₃CH₂ 544 CF₃CF₂CH₂CH₂ CF₃CH₂545 CF₃CF₂CF₂CH₂ CF₃CH₂ 546 CF₂═C(CH₃)CH₂CH₂ CF₃CH₂ 547 CH₃CH₂CH₂CH₂CH₂CF₃CH₂ 548 CH₃CH₂CH₂CH₂(CH₃)CH CF₃CH₂ 549 CH₃CH₂CH₂(CH₃)CHCH₂ CF₃CH₂ 550CH₃CH₂(CH₃)CHCH₂CH₂ CF₃CH₂ 551 CH₃CH₂CH₂(CH₃)CH(CH₃)CH CF₃CH₂ 552CH₃CH₂(CH₃)CHCH₂(CH₃)CH CF₃CH₂ 553 HOCH₂CH₂ CF₃CH₂ 554 CH₃OCH₂CH₂ CF₃CH₂555 CH₃OCH₂(CH₃)CH CF₃CH₂ 556 CH₃OCH₂(CF₃)CH CF₃CH₂ 557 CH₃OCH₂(CH₃)₂CCF₃CH₂ 558 CH₃O(CH₃)CHCH₂ CF₃CH₂ 559 CH₃O(CH₃)CH(CH₃)CH CF₃CH₂ 560HC≡CCH₂ CF₃CH₂ 561 CH₃C≡CCH₂ CF₃CH₂ 562 HC≡CCH₂CH₂ CF₃CH₂ 563HOCH₂CH₂CH₂ CF₃CH₂ 564 CH₃OCH₂CH₂CH₂ CF₃CH₂ 565 (CH₃)₃SiCH₂ CF₃CH₂ 566C₆H₅CH₂ CF₃CH₂ 567 C₆H₅(CH₃)CH CF₃CH₂ 568 4-F—C₆H₄CH₂ CF₃CH₂ 5694-Cl—C₆H₄CH₂ CF₃CH₂ 570 4-F—C₆H₅(CH₃)CH CF₃CH₂ 571 4-Cl—C₆H₅(CH₃)CHCF₃CH₂ 572 C₆H₅CH₂CH₂ CF₃CH₂ 573 4-F—C₆H₅CH₂CH₂ CF₃CH₂ 574 1-piperidinoCF₃CH₂ 575 1-pyrrolidino CF₃CH₂ 576 cyclo-C₅H₉CH₂ CF₃CH₂ 577bicyclo[2.2.1]hept-2-yl CF₃CH₂ 578 1-CH₃-cyclopropyl CF₃CH₂ 579cis-2-CH₃-cyclopropyl CF₃CH₂ 580 trans-2-CH₃-cyclopropyl CF₃CH₂ 5812,2-(CH₃)₂-cyclopropyl CF₃CH₂ 582 1-CH₃-cyclobutyl CF₃CH₂ 583cis-2-CH₃-cyclobutyl CF₃CH₂ 584 trans-2-CH₃-cyclobutyl CF₃CH₂ 585cis-3-CH₃-cyclobutyl CF₃CH₂ 586 trans-3-CH₃-cyclobutyl CF₃CH₂ 5872,2-(CH₃)₂-cyclobutyl CF₃CH₂ 588 3,3-(CH₃)₂-cyclobutyl CF₃CH₂ 5891-CH₃-cyclopentyl CF₃CH₂ 590 cis-2-CH₃-cyclopentyl CF₃CH₂ 591trans-2-CH₃-cyclopentyl CF₃CH₂ 592 cis-3-CH₃-cyclopentyl CF₃CH₂ 593trans-3-CH₃-cyclopentyl CF₃CH₂ 594 2,2-(CH₃)₂-cyclopentyl CF₃CH₂ 5953,3-(CH₃)₂-cyclopentyl CF₃CH₂ 596 1-CH₃-cyclohexyl CF₃CH₂ 597cis-2-CH₃-cyclohexyl CF₃CH₂ 598 trans-2-CH₃-cyclohexyl CF₃CH₂ 599cis-3-CH₃-cyclohexyl CF₃CH₂ 600 trans-3-CH₃-cyclohexyl CF₃CH₂ 6012,2-(CH₃)₂-cyclohexyl CF₃CH₂ 602 3,3-(CH₃)₂-cyclohexyl CF₃CH₂ 603cis-4-CH₃-cyclohexyl CF₃CH₂ 604 trans-4-CH₃-cyclohexyl CF₃CH₂ 6054,4-(CH₃)₂-cyclohexyl CF₃CH₂ 606 4-(CH₃)₃C-cyclohexyl CF₃CH₂ 607cis-1-CH₃-2-fluorocyclopropyl H 608 trans-1-CH₃-2-fluorocyclopropyl H609 1-CH₃-2,2-difluorocyclopropyl H 610cis-1-CH₃-2-chloro-2-fluorocyclopropyl H 611trans-1-CH₃-2-chloro-2-fluorocyclopropyl H 612 CH₃CO(CH₃)CH H 613CH₃CH₂CO(CH₃)CH H 614 (CH₃)₂CHCO(CH₃)CH H 615 (CH₃)₃CCO(CH₃)CH H 616CH₃CH₂CH₂CO(CH₃)CH H 617 CH₃CO(CF₃)CH H 618 CH₃CH₂CO(CF₃)CH H 619CH₃CO(CH₃)₂C H 620 CH₃CH₂CO(CH₃)₂C H 621 cis-1-CH₃-2-fluorocyclopropylCH₃ 622 trans-1-CH₃-2-fluorocyclopropyl CH₃ 6231-CH₃-2,2-difluorocyclopropyl CH₃ 624cis-1-CH₃-2-chloro-2-fluorocyclopropyl CH₃ 625trans-1-CH₃-2-chloro-2-fluorocyclopropyl CH₃ 626 CH₃CO(CH₃)CH CH₃ 627CH₃CH₂CO(CH₃)CH CH₃ 628 (CH₃)₂CHCO(CH₃)CH CH₃ 629 (CH₃)₃CCO(CH₃)CH CH₃630 CH₃CH₂CH₂CO(CH₃)CH CH₃ 631 CH₃CO(CF₃)CH CH₃ 632 CH₃CH₂CO(CF₃)CH CH₃633 CH₃CO(CH₃)₂C CH₃ 634 CH₃CH₂CO(CH₃)₂C CH₃ 635cis-1-CH₃-2-fluorocyclopropyl C₂H₅ 636 trans-1-CH₃-2-fluorocyclopropylC₂H₅ 637 1-CH₃-2,2-difluorocyclopropyl C₂H₅ 638cis-1-CH₃-2-chloro-2-fluorocyclopropyl C₂H₅ 639trans-1-CH₃-2-chloro-2-fluorocyclopropyl C₂H₅ 640 CH₃CO(CH₃)CH C₂H₅ 641CH₃CH₂CO(CH₃)CH C₂H₅ 642 (CH₃)₂CHCO(CH₃)CH C₂H₅ 643 (CH₃)₃CCO(CH₃)CHC₂H₅ 644 CH₃CH₂CH₂CO(CH₃)CH C₂H₅ 645 CH₃CO(CF₃)CH C₂H₅ 646CH₃CH₂CO(CF₃)CH C₂H₅ 647 CH₃CO(CH₃)₂C C₂H₅ 648 CH₃CH₂CO(CH₃)₂C C₂H₅ 649cis-1-CH₃-2-fluorocyclopropyl CF₃CH₂ 650 trans-1-CH₃-2-fluorocyclopropylCF₃CH₂ 651 1-CH₃-2,2-difluorocyclopropyl CF₃CH₂ 652cis-1-CH₃-2-chloro-2-fluorocyclopropyl CF₃CH₂ 653trans-1-CH₃-2-chloro-2-fluorocyclopropyl CF₃CH₂ 654 CH₃CO(CH₃)CH CF₃CH₂655 CH₃CH₂CO(CH₃)CH CF₃CH₂ 656 (CH₃)₂CHCO(CH₃)CH CF₃CH₂ 657(CH₃)₃CCO(CH₃)CH CF₃CH₂ 658 CH₃CH₂CH₂CO(CH₃)CH CF₃CH₂ 659 CH₃CO(CF₃)CHCF₃CH₂ 660 CH₃CH₂CO(CF₃)CH CF₃CH₂ 661 CH₃CO(CH₃)₂C CF₃CH₂ 662CH₃CH₂CO(CH₃)₂C CF₃CH₂Table 2

Table 2 consists of 662 compounds of the general formula (1A), where Wand Z are N, X and Y are CH, R is Cl, R¹ is 2,5,6-trifluorophenyl, andthe values of R³ and R⁴ are as listed in Table 1. Thus, compound 1 ofTable 2 is the same as compound 1 of Table 1 except that in compound 1of Table 2, R¹ is 2,5,6-trifluorophenyl. Similarly, compounds 2 to 662of Table 2 are the same as compounds 2 to 662 of Table 1 except that inthe compounds of Table 2, R¹ is 2,5,6-trifluorophenyl.

Table 3

Table 3 consists of 662 compounds of the general formula (1A), where Wand Z are N, X and Y are CH, R is Cl, R¹ is 2,3,4,5,6-pentafluorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 3 is the same as compound 1 of Table 1 except that in compound1 of Table 3, R¹ is 2,3,4,5,6-pentafluorophenyl. Similarly, compounds 2to 662 of Table 3 are the same as compounds 2 to 662 of Table 1 exceptthat in the compounds of Table 3, R¹ is 2,3,4,5,6-pentafluorophenyl.

Table 4

Table 4 consists of 662 compounds of the general formula (1A), where Wand Z are N, X and Y are CH, R is Cl, R¹ is2,6-difluoro-4-methoxyphenyl, and the values of R³ and R⁴ are as listedin Table 1. Thus, compound 1 of Table 4 is the same as compound 1 ofTable 1 except that in compound 1 of Table 4, R¹ is2,6-difluoro-4-methoxyphenyl. Similarly, compounds 2 to 662 of Table 4are the same as compounds 2 to 662 of Table 1 except that in thecompounds of Table 4, R¹ is 2,6-difluoro-4-methoxyphenyl.

Table 5

Table 5 consists of 662 compounds of the general formula (1A), where Wand Z are N, X and Y are CH, R is Cl, R¹ is 2-fluoro-6-chlorophenyl, andthe values of R³ and R⁴ are as listed in Table 1. Thus, compound 1 ofTable 5 is the same as compound 1 of Table 1 except that in compound 1of Table 5, R¹ is 2-fluoro-6-chlorophenyl. Similarly, compounds 2 to 662of Table 5 are the same as compounds 2 to 662 of Table 1 except that inthe compounds of Table 5, R¹ is 2-fluoro-6-chlorophenyl. TABLE 6 (1B)

Table 6 consists of 662 compounds of the general formula (1B), where Wand Z are N, X and Y are CH, R is Cl, R¹ is 2,4,6-trifluorophenyl, andthe values of R³ and R⁴ are as listed in Table 1. Thus, compound 1 ofTable 6 is the same as compound 1 of Table 1 except that in compound 1of Table 6, the compound has the general formula (1B). Similarly,compounds 2 to 662 of Table 6 are the same as compounds 2 to 662 ofTable 1 except that in the compounds of Table 6, the compounds have thegeneral formula (1B).

Table 7

Table 7 consists of 662 compounds of the general formula (1B), where Wand Z are N, X and Y are CH, R is Cl, R¹ is 2,5,6-trifluorophenyl, andthe values of R³ and R⁴ are as listed in Table 1. Thus, compound 1 ofTable 7 is the same as compound 1 of Table 2 except that in compound 1of Table 7, the compound has the general formula (1B). Similarly,compounds 2 to 662 of Table 7 are the same as compounds 2 to 662 ofTable 2 except that in the compounds of Table 7, the compounds have thegeneral formula (1B).

Table 8

Table 8 consists of 662 compounds of the general formula (1B), where Wand Z are N, X and Y are CH, R is Cl, R¹ is 2,3,4,5,6-pentafluorophenyl,and the values of R³ and R⁴ are as listed in Table 3. Thus, compound 1of Table 8 is the same as compound 1 of Table 3 except that in compound1 of Table 8, the compound has the general formula (1B). Similarly,compounds 2 to 662 of Table 8 are the same as compounds 2 to 662 ofTable 3 except that in the compounds of Table 8, the compounds have thegeneral formula (1B).

Table 9

Table 9 consists of 662 compounds of the general formula (I B), where Wand Z are N, X and Y are CH, R is Cl, R¹ is2,6-difluoro-4-methoxyphenyl, and the values of R³ and R⁴ are as listedin Table 1. Thus, compound 1 of Table 9 is the same as compound 1 ofTable 4 except that in compound 1 of Table 9, the compound has thegeneral formula (1B). Similarly, compounds 2 to 662 of Table 9 are thesame as compounds 2 to 662 of Table 4 except that in the compounds ofTable 9, the compounds have the general formula (1B).

Table 10

Table 10 consists of 662 compounds of the general formula (1B), where Wand Z are N, X and Y are CH, R is Cl, R¹ is 2-fluoro-6-chlorophenyl, andthe values of R³ and R⁴ are as listed in Table 1. Thus, compound 1 ofTable 10 is the same as compound 1 of Table 5 except that in compound 1of Table 10, the compound has the general formula (1B). Similarly,compounds 2 to 662 of Table 10 are the same as compounds 2 to 662 ofTable 5 except that in the compounds of Table 10, the compounds have thegeneral formula (1B).

Table 11

Table 11 consists of 662 compounds of the general formula (1A), where Wand X are N and Y and Z are CH, R is Cl, R¹ is 2,4,6-trifluorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 11 is the same as compound 1 of Table 1 except that in compound1 of Table 11, the compound has the general formula (1A) where W and Xare N and Y and Z are CH. Similarly, compounds 2 to 662 of Table 11 arethe same as compounds 2 to 662 of Table 1 except that in the compoundsof Table 11, the compounds have the general formula (1A) where W and Xare N and Y and Z are CH.

Table 12

Table 12 consists of 662 compounds of the general formula (1A), where Wand X are N and Y and Z are CH, R is Cl, R¹ is 2,5,6-trifluorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 12 is the same as compound 1 of Table 2 except that in compound1 of Table 12, the compound has the general formula (1A) where W and Xare N and Y and Z are CH. Similarly, compounds 2 to 662 of Table 12 arethe same as compounds 2 to 662 of Table 2 except that in the compoundsof Table 12, the compounds have the general formula (1A) where W and Xare N and Y and Z are CH.

Table 13

Table 13 consists of 662 compounds of the general formula (1A), where Wand X are N and Y and Z are CH, R is Cl, R¹ is2,3,4,5,6-pentafluorophenyl, and the values of R³ and R⁴ are as listedin Table 1. Thus, compound 1 of Table 13 is the same as compound 1 ofTable 3 except that in compound 1 of Table 13, the compound has thegeneral formula (1A) where W and X are N and Y and Z are CH. Similarly,compounds 2 to 662 of Table 13 are the same as compounds 2 to 662 ofTable 3 except that in the compounds of Table 13, the compounds have thegeneral formula (1A) where W and X are N and Y and Z are CH.

Table 14

Table 14 consists of 662 compounds of the general formula (1A), where Wand X are N and Y and Z are CH, R is Cl, R¹ is2,6-difluoro-4-methoxyphenyl, and the values of R³ and R⁴ are as listedin Table 1. Thus, compound 1 of Table 14 is the same as compound 1 ofTable 4 except that in compound 1 of Table 14, the compound has thegeneral formula (1A) where W and X are N and Y and Z are CH. Similarly,compounds 2 to 662 of Table 14 are the same as compounds 2 to 662 ofTable 4 except that in the compounds of Table 14, the compounds have thegeneral formula (1A) where W and X are N and Y and Z are CH.

Table 15

Table 15 consists of 662 compounds of the general formula (1A), where Wand X are N and Y and Z are CH, R is Cl, R¹ is 2-fluoro-6-chlorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 15 is the same as compound 1 of Table 5 except that in compound1 of Table 15, the compound has the general formula (1A) where W and Xare N and Y and Z are CH. Similarly, compounds 2 to 662 of Table 15 arethe same as compounds 2 to 662 of Table 5 except that in the compoundsof Table 15, the compounds have the general formula (1A) where W and Xare N and Y and Z are CH.

Table 16

Table 16 consists of 662 compounds of the general formula (1B), where Wand X are N and Y and Z are CH, R is Cl, R¹ is 2,4,6-trifluorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 16 is the same as compound 1 of Table 11 except that incompound 1 of Table 16, the compound has the general formula (1B).Similarly, compounds 2 to 662 of Table 16 are the same as compounds 2 to662 of Table 11 except that in the compounds of Table 16, the compoundshave the general formula (1B).

Table 17

Table 17 consists of 662 compounds of the general formula (1B), where Wand X are N and Y and Z are CH, R is Cl, R¹ is 2,5,6-trifluorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 17 is the same as compound 1 of Table 12 except that incompound 1 of Table 17, the compound has the general formula (1B).Similarly, compounds 2 to 662 of Table 17 are the same as compounds 2 to662 of Table 12 except that in the compounds of Table 17, the compoundshave the general formula (1B).

Table 18

Table 18 consists of 662 compounds of the general formula (1B), where Wand X are N and Y and Z are CH, R is Cl, R¹ is2,3,4,5,6-pentafluorophenyl, and the values of R³ and R⁴ are as listedin Table 1. Thus, compound 1 of Table 18 is the same as compound 1 ofTable 13 except that in compound 1 of Table 18, the compound has thegeneral formula (1B). Similarly, compounds 2 to 662 of Table 18 are thesame as compounds 2 to 662 of Table 13 except that in the compounds ofTable 18, the compounds have the general formula (1B).

Table 19

Table 19 consists of 662 compounds of the general formula (1B), where Wand X are N and Y and Z are CH, R is Cl, R¹ is2,6-difluoro-4-methoxyphenyl, and the values of R³ and R⁴ are as listedin Table 1. Thus, compound 1 of Table 19 is the same as compound 1 ofTable 14 except that in compound 1 of Table 19, the compound has thegeneral formula (1B). Similarly, compounds 2 to 662 of Table 19 are thesame as compounds 2 to 662 of Table 14 except that in the compounds ofTable 19, the compounds have the general formula (1B).

Table 20

Table 20 consists of 662 compounds of the general formula (1B), where Wand X are N and Y and Z are CH, R is Cl, R¹ is 2-fluoro-6-chlorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 20 is the same as compound 1 of Table 15 except that incompound 1 of Table 20, the compound has the general formula (1B).Similarly, compounds 2 to 662 of Table 20 are the same as compounds 2 to662 of Table 15 except that in the compounds of Table 20, the compoundshave the general formula (1B).

Table 21

Table 21 consists of 662 compounds of the general formula (1A), where Wand Z are CH and X and Y are N, R is Cl, R¹ is 2,4,6-trifluorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 21 is the same as compound 1 of Table 1 except that in compound1 of Table 21, the compound has the general formula (1A) where W and Zare CH and X and Y are N. Similarly, compounds 2 to 662 of Table 21 arethe same as compounds 2 to 662 of Table 1 except that in the compoundsof Table 21, the compounds have the general formula (1A) where W and Zare CH and X and Y are N.

Table 22

Table 22 consists of 662 compounds of the general formula (1A), where Wand Z are CH and X and Y are N, R is Cl, R¹ is 2,5,6-trifluorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 22 is the same as compound 1 of Table 2 except that in compound1 of Table 22, the compound has the general formula (1A) where W and Zare CH and X and Y are N. Similarly, compounds 2 to 662 of Table 22 arethe same as compounds 2 to 662 of Table 2 except that in the compoundsof Table 22, the compounds have the general formula (1A) where W and Zare CH and X and Y are N.

Table 23

Table 23 consists of 662 compounds of the general formula (1A), where Wand Z are CH and X and Y are N, R is Cl, R¹ is2,3,4,5,6-pentafluorophenyl, and the values of R³ and R⁴ are as listedin Table 1. Thus, compound 1 of Table 23 is the same as compound 1 ofTable 3 except that in compound 1 of Table 23, the compound has thegeneral formula (1A) where W and Z are CH and X and Y are N. Similarly,compounds 2 to 662 of Table 23 are the same as compounds 2 to 662 ofTable 3 except that in the compounds of Table 23, the compounds have thegeneral formula (1A) where W and Z are CH and X and Y are N.

Table 24

Table 24 consists of 662 compounds of the general formula (1A), where Wand Z are CH and X and Y are N, R is Cl, R¹ is2,6-difluoro-4-methoxyphenyl, and the values of R³ and R⁴ are as listedin Table 1. Thus, compound 1 of Table 24 is the same as compound 1 ofTable 4 except that in compound 1 of Table 24, the compound has thegeneral formula (1A) where W and Z are CH and X and Y are N. Similarly,compounds 2 to 662 of Table 24 are the same as compounds 2 to 662 ofTable 4 except that in the compounds of Table 24, the compounds have thegeneral formula (1A) where W and Z are CH and X and Y are N.

Table 25

Table 25 consists of 662 compounds of the general formula (1A), where Wand Z are CH and X and Y are N, R is Cl, R¹ is 2-fluoro-6-chlorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 25 is the same as compound 1 of Table 5 except that in compound1 of Table 25, the compound has the general formula (1A) where W and Zare CH and X and Y are N. Similarly, compounds 2 to 662 of Table 25 arethe same as compounds 2 to 662 of Table 5 except that in the compoundsof Table 25, the compounds have the general formula (1A) where W and Zare CH and X and Y are N.

Table 26

Table 26 consists of 662 compounds of the general formula (1A), where Wand X are CH and Y and Z are N, R is Cl, R¹ is 2,4,6-trifluorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 26 is the same as compound 1 of Table 1 except that in compound1 of Table 26, the compound has the general formula (1A) where W and Xare CH and Y and Z are N. Similarly, compounds 2 to 662 of Table 26 arethe same as compounds 2 to 662 of Table 1 except that in the compoundsof Table 26, the compounds have the general formula (1A) where W and Xare CH and Y and Z are N.

Table 27

Table 27 consists of 662 compounds of the general formula (1A), where Wand X are CH and Y and Z are N, R is Cl, R¹ is 2,5,6-trifluorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 27 is the same as compound 1 of Table 2 except that in compound1 of Table 27, the compound has the general formula (1A) where W and Xare CH and Y and Z are N. Similarly, compounds 2 to 662 of Table 27 arethe same as compounds 2 to 662 of Table 2 except that in the compoundsof Table 27, the compounds have the general formula (1A) where W and Xare CH and Y and Z are N.

Table 28

Table 28 consists of 662 compounds of the general formula (1A), where Wand X are CH and Y and Z are N, R is Cl, R¹ is2,3,4,5,6-pentafluorophenyl, and the values of R³ and R⁴ are as listedin Table 1. Thus, compound 1 of Table 28 is the same as compound 1 ofTable 3 except that in compound 1 of Table 28, the compound has thegeneral formula (1A) where W and X are CH and Y and Z are N. Similarly,compounds 2 to 662 of Table 28 are the same as compounds 2 to 662 ofTable 3 except that in the compounds of Table 28, the compounds have thegeneral formula (1A) where W and X are CH and Y and Z are N.

Table 29

Table 29 consists of 662 compounds of the general formula (1A), where Wand X are CH and Y and Z are N, R is Cl, R¹ is2,6-difluoro-4-methoxyphenyl, and the values of R³ and R⁴ are as listedin Table 1. Thus, compound 1 of Table 29 is the same as compound 1 ofTable 4 except that in compound 1 of Table 29, the compound has thegeneral formula (1A) where W and X are CH and Y and Z are N. Similarly,compounds 2 to 662 of Table 29 are the same as compounds 2 to 662 ofTable 4 except that in the compounds of Table 29, the compounds have thegeneral formula (1A) where W and X are CH and Y and Z are N.

Table 30

Table 30 consists of 662 compounds of the general formula (1A), where Wand X are CH and Y and Z are N, R is Cl, R¹ is 2-fluoro-6-chlorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 30 is the same as compound 1 of Table 5 except that in compound1 of Table 30, the compound has the general formula (1A) where W and Xare CH and Y and Z are N. Similarly, compounds 2 to 662 of Table 30 arethe same as compounds 2 to 662 of Table 5 except that in the compoundsof Table 30, the compounds have the general formula (1A) where W and Xare CH and Y and Z are N.

Table 31

Table 31 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 31 R¹ is 2,6-difluorophenyl instead of2-fluoro-6-chlorophenyl.

Table 32

Table 32 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 32 R¹ is 2-fluorophenyl instead of2-fluoro-6-chlorophenyl.

Table 33

Table 33 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 33 R¹ is 2,3,5,6-tetrafluorophenyl instead of2-fluoro-6-chlorophenyl.

Table 34

Table 34 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 34 R¹ is 2-chloro-4,6-difluorophenyl instead of2-fluoro-6-chlorophenyl.

Table 35

Table 35 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 35 R¹ is 2-chlorophenyl instead of2-fluoro-6-chlorophenyl.

Table 36

Table 36 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 36 R¹ is 2,6-dichlorophenyl instead of2-fluoro-6-chlorophenyl.

Table 37

Table 37 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 37 R¹ is 2,4-dichlorophenyl instead of2-fluoro-6-chlorophenyl.

Table 38

Table 38 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 38 R¹ is 2,4,6-trichlorophenyl instead of2-fluoro-6-chlorophenyl.

Table 39

Table 39 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 39 R¹ is 2,3,6-trichlorophenyl instead of2-fluoro-6-chlorophenyl.

Table 40

Table 40 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 40 R¹ is pentachlorophenyl instead of2-fluoro-6-chlorophenyl.

Table 41

Table 41 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 41 R¹ is 2-fluoro-4,6-dichlorophenyl instead of2-fluoro-6-chlorophenyl.

Table 42

Table 42 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 42 R¹ is 4-fluoro-2,6-dichlorophenyl instead of2-fluoro-6-chlorophenyl.

Table 43

Table 43 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 43 R¹ is 2-bromophenyl instead of2-fluoro-6-chlorophenyl.

Table 44

Table 44 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 44 R¹ is 2-fluoro-6-bromophenyl instead of2-fluoro-6-chlorophenyl.

Table 45

Table 45 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 45 R¹ is 2-bromo-4,6-difluorophenyl instead of2-fluoro-6-chlorophenyl.

Table 46

Table 46 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 46 R¹ is 2-fluoro-6-methylphenyl instead of2-fluoro-6-chlorophenyl.

Table 47

Table 47 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 47 R¹ is 2-chloro-6-methylphenyl instead of2-fluoro-6-chlorophenyl.

Table 48

Table 48 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 48 R¹ is 2-methoxyphenyl instead of2-fluoro-6-chlorophenyl.

Table 49

Table 49 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 49 R¹ is 2,6-dimethoxyphenyl instead of2-fluoro-6-chlorophenyl.

Table 50

Table 50 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 50 R¹ is 2-fluoro-6-methoxyphenyl instead of2-fluoro-6-chlorophenyl.

Table 51

Table 51 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 51 R¹ is 2-trifluoromethylphenyl instead of2-fluoro-6-chlorophenyl.

Table 52

Table 52 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 52 R¹ is 2-fluoro-6-trifluoromethylphenyl instead of2-fluoro-6-chlorophenyl.

Table 53

Table 53 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 53 R¹ is 2,6-di-(trifluoromethyl)phenyl instead of2-fluoro-6-chlorophenyl.

Table 54

Table 54 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 54 R¹ is 2-chloro-6-trifluoromethylphenyl instead of2-fluoro-6-chlorophenyl.

Table 55

Table 55 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 55 R¹ is 2,4-difluoro-6-trifluoromethylphenyl insteadof 2-fluoro-6-chlorophenyl.

Table 56

Table 56 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 56 R¹ is 2,4-difluoro-6-methoxyphenyl instead of2-fluoro-6-chlorophenyl.

Table 57

Table 57 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 57 R¹ is 2,4-difluoro-6-methylphenyl instead of2-fluoro-6-chlorophenyl.

Table 58

Table 58 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 58 R¹ is 2,4-difluoropyrid-3-yl instead of2-fluoro-6-chlorophenyl.

Table 59

Table 59 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 59 R¹ is 3,5-difluoropyrid-4-yl instead of2-fluoro-6-chlorophenyl.

Table 60

Table 60 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 60 R¹ is tetrafluoropyrid-4-yl instead of2-fluoro-6-chlorophenyl.

Table 61

Table 61 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 61 R¹ is 3-fluoropyrid-2-yl instead of2-fluoro-6-chlorophenyl.

Table 62

Table 62 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 62 R¹ is 4-fluoropyrid-3-yl instead of2-fluoro-6-chlorophenyl.

Table 63

Table 63 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 63 R¹ is 3-fluoropyrid-4-yl instead of2-fluoro-6-chlorophenyl.

Table 64

Table 64 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 64 R¹ is 2-fluoropyrid-3-yl instead of2-fluoro-6-chlorophenyl.

Table 65

Table 65 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 65 R¹ is 2,4,6-trifluoropyrid-3-yl instead of2-fluoro-6-chlorophenyl.

Table 66

Table 66 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 66 R¹ is 3,5-difluoropyrid-2-yl instead of2-fluoro-6-chlorophenyl.

Table 67

Table 67 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 67 R¹ is 2,6-difluoropyrid-3-yl instead of2-fluoro-6-chlorophenyl.

Table 68

Table 68 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 68 R¹ is 2,4-difluoro-6-methoxypyrid-3-yl instead of2-fluoro-6-chlorophenyl.

Table 69

Table 69 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 69 R¹ is 2-fluoro-4-chloropyrid-3-yl instead of2-fluoro-6-chlorophenyl.

Table 70

Table 70 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 70 R¹ is 3-fluoro-5-chloropyrid-4-yl instead of2-fluoro-6-chlorophenyl.

Table 71

Table 71 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 71 R¹ is 2-chloro-4-fluoropyrid-3-yl instead of2-fluoro-6-chlorophenyl.

Table 72

Table 72 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 72 R¹ is 2,4-dichloropyrid-3-yl instead of2-fluoro-6-chlorophenyl.

Table 73

Table 73 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 73 R¹ is 3-chloropyrid-2-yl instead of2-fluoro-6-chlorophenyl.

Table 74

Table 74 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 74 R¹ is 4-chloropyrid-3-yl instead of2-fluoro-6-chlorophenyl.

Table 75

Table 75 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 75 R¹ is 3-chloropyrid-4-yl instead of2-fluoro-6-chlorophenyl.

Table 76

Table 76 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 76 R¹ is 2-chloropyrid-3-yl instead of2-fluoro-6-chlorophenyl.

Table 77

Table 77 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 77 R¹ is 3-trifluoromethylpyrid-2-yl instead of2-fluoro-6-chlorophenyl.

Table 78

Table 78 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 78 R¹ is 4-trifluoromethylpyrid-3-yl instead of2-fluoro-6-chlorophenyl.

Table 79

Table 79 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 79 R¹ is 3,5-dichloropyrid-2-yl instead of2-fluoro-6-chlorophenyl.

Table 80

Table 80 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 80 R¹ is 4,6-dichloropyrid-3-yl instead of2-fluoro-6-chlorophenyl.

Table 81

Table 81 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 81 R¹ is 3-trifluoromethylpyrid-4-yl instead of2-fluoro-6-chlorophenyl.

Table 82

Table 82 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 82 R¹ is 2-trifluoromethylpyrid-3-yl instead of2-fluoro-6-chlorophenyl.

Table 83

Table 83 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 83 R¹ is 2-fluoro-4-trifluoromethylpyrid-3-yl insteadof 2-fluoro-6-chlorophenyl.

Table 84

Table 84 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 84 R¹ is 3-fluoro-5-trifluoromethylpyrid-4-yl insteadof 2-fluoro-6-chlorophenyl.

Table 85

Table 85 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 85 R¹ is 4-fluoro-2-trifluoromethylpyrid-3-yl insteadof 2-fluoro-6-chlorophenyl.

Table 86

Table 86 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 86 R¹ is 2,6-dichloropyrid-3-yl instead of2-fluoro-6-chlorophenyl.

Table 87

Table 87 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 87 R¹ is 3,5-dichloropyrid-4-yl instead of2-fluoro-6-chlorophenyl.

Table 88

Table 88 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 88 R¹ is 3-chloro-6-trifluoromethylpyrid-2-yl insteadof 2-fluoro-6-chlorophenyl.

Table 89

Table 89 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 89 R¹ is 3-fluoro-6-trifluoromethylpyrid-2-yl insteadof 2-fluoro-6-chlorophenyl.

Table 90

Table 90 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 90 R¹ is pyrid-2-yl instead of2-fluoro-6-chlorophenyl.

Table 91

Table 91 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 91 R¹ is pyrid-3-yl instead of2-fluoro-6-chlorophenyl.

Table 92

Table 92 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 92 R¹ is pyrid-4-yl instead of2-fluoro-6-chlorophenyl.

Table 93

Table 93 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 93 R¹ is 3-fluorothien-2-yl instead of2-fluoro-6-chlorophenyl.

Table 94

Table 94 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 94 R¹ is 3-chlorothien-2-yl instead of2-fluoro-6-chlorophenyl.

Table 95

Table 95 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 95 R¹ is 2,4-difluorothien-3-yl instead of2-fluoro-6-chlorophenyl.

Table 96

Table 96 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 96 R¹ is 2,4-dichlorothien-3-yl instead of2-fluoro-6-chlorophenyl.

Table 97

Table 97 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 97 R¹ is 2,4,5-trichlorothien-3-yl instead of2-fluoro-6-chlorophenyl.

Table 98

Table 98 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 98 R¹ is piperidino instead of2-fluoro-6-chlorophenyl.

Table 99

Table 99 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 99 R¹ is 2-methylpiperidino instead of2-fluoro-6-chlorophenyl.

Table 100

Table 100 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 100 R¹ is 2,6-dimethylpiperidino instead of2-fluoro-6-chlorophenyl.

Table 101

Table 101 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 101 R¹ is morpholino instead of2-fluoro-6-chlorophenyl.

Table 102

Table 102 consists of 3972 compounds. Compounds 1 to 662 are exactly thesame as compounds 1 to 662 of Table 5 respectively, compounds 663 to1324 are exactly the same as compounds 1 to 662 of Table 10respectively, compounds 1325 to 1986 are exactly the same as compounds 1to 662 of Table 15 respectively, compounds 1987 to 2648 are exactly thesame as compounds 1 to 662 of Table 20 respectively, compounds 2649 to3310 are exactly the same as compounds 1 to 662 of Table 25respectively, and compounds 3311 to 3972 are exactly the same ascompounds 1 to 662 of Table 30 respectively, except that in all of thecompounds of Table 102 R¹ is 2,6-dimethylmorpholino instead of2-fluoro-6-chlorophenyl.

Table 103

Table 103 consists of 305,844 compounds. Each of these compounds isexactly the same as the corresponding compound in Tables 1 to 102 (thus,for example, compound 1 of Table 103 is the same as compound 1 of Table1, compound 663 of Table 103 is the same as compound 1 of Table 2,compound 19,861 of Table 103 is the same as compound 1 of Table 31,compound 305,844 of Table 103 is the same as compound 3,972 of Table102) except that in all of the compounds of Table 103 R is F instead ofCl.

Table 104

Table 104 consists of 305,844 compounds. Each of these compounds isexactly the same as the corresponding compound in Tables 1 to 102 (thus,for example, compound 1 of Table 104 is the same as compound 1 of Table1, compound 663 of Table 104 is the same as compound 1 of Table 2,compound 19,861 of Table 104 is the same as compound 1 of Table 31,compound 305,844 of Table 104 is the same as compound 3,972 of Table102) except that in all of the compounds of Table 104 R is Br instead ofCl.

Table 105

Table 105 consists of 305,844 compounds. Each of these compounds isexactly the same as the corresponding compound in Tables 1 to 102 (thus,for example, compound 1 of Table 105 is the same as compound 1 of Table1, compound 663 of Table 105 is the same as compound 1 of Table 2,compound 19,861 of Table 105 is the same as compound 1 of Table 31,compound 305,844 of Table 105 is the same as compound 3,972 of Table102) except that in all of the compounds of Table 105 R is methylinstead of Cl.

Table 106

Table 106 consists of 305,844 compounds. Each of these compounds isexactly the same as the corresponding compound in Tables 1 to 102 (thus,for example, compound 1 of Table 106 is the same as compound 1 of Table1, compound 663 of Table 106 is the same as compound 1 of Table 2,compound 19,861 of Table 106 is the same as compound 1 of Table 31,compound 305,844 of Table 106 is the same as compound 3,972 of Table102) except that in all of the compounds of Table 106 R is H instead ofCl.

Table 107

Table 107 consists of 305,844 compounds. Each of these compounds isexactly the same as the corresponding compound in Tables 1 to 102 (thus,for example, compound 1 of Table 107 is the same as compound 1 of Table1, compound 663 of Table 107 is the same as compound 1 of Table 2,compound 19,861 of Table 107 is the same as compound 1 of Table 31,compound 305,844 of Table 107 is the same as compound 3,972 of Table102) except that in all of the compounds of Table 107 R is cyano insteadof Cl.

Table 108

Table 108 consists of 305;844 compounds. Each of these compounds isexactly the same as the corresponding compound in Tables 1 to 102 (thus,for example, compound 1 of Table 108 is the same as compound 1 of Table1, compound 663 of Table 108 is the same as compound 1 of Table 2,compound 19,861 of Table 108 is the same as compound 1 of Table 31,compound 305,844 of Table 108 is the same as compound 3,972 of Table102) except that in all of the compounds of Table 108 R is methoxyinstead of Cl.

Table 109

Table 109 consists of 6620 compounds. Each of these compounds is exactlythe same as the corresponding compound in Tables 1 to 10 (thus, forexample, compound 1 of Table 109 is the same as compound 1 of Table 1,compound 663 of Table 109 is the same as compound 1 of Table 2, etc.)except that in all of the compounds of Table 109 X is CF instead of CH.

Table 110

Table 110 consists of 6620 compounds. Each of these compounds is exactlythe same as the corresponding compound in Tables 1 to 10 (thus, forexample, compound 1 of Table 110 is the same as compound 1 of Table 1,compound 663 of Table 110 is the same as compound 1 of Table 2, etc.)except that in all of the compounds of Table 110 X is CCl instead of CH.

Table 111

Table 111 consists of 6620 compounds. Each of these compounds is exactlythe same as the corresponding compound in Tables 1 to 10 (thus, forexample, compound 1 of Table 111 is the same as compound 1 of Table 1,compound 663 of Table 111 is the same as compound 1 of Table 2, etc.)except that in all of the compounds of Table 111 X is CBr instead of CH.

Table 112

Table 112 consists of 6620 compounds. Each of these compounds is exactlythe same as the corresponding compound in Tables 1 to 10 (thus, forexample, compound 1 of Table 112 is the same as compound 1 of Table 1,compound 663 of Table 112 is the same as compound 1 of Table 2, etc.)except that in all of the compounds of Table 112 X is CCH₃ instead ofCH.

Table 113

Table 113 consists of 6620 compounds. Each of these compounds is exactlythe same as the corresponding compound in Tables 1 to 10 (thus, forexample, compound 1 of Table 113 is the same as compound 1 of Table 1,compound 663 of Table 113 is the same as compound 1 of Table 2, etc.)except that in all of the compounds of Table 113 Y is CF instead of CH.

Table 114

Table 114 consists of 6620 compounds. Each of these compounds is exactlythe same as the corresponding compound in Tables 1 to 10 (thus, forexample, compound 1 of Table 114 is the same as compound 1 of Table 1,compound 663 of Table 114 is the same as compound 1 of Table 2, etc.)except that in all of the compounds of Table 114 Y is CCl instead of CH.

Table 115

Table 115 consists of 6620 compounds. Each of these compounds is exactlythe same as the corresponding compound in Tables 1 to 10 (thus, forexample, compound 1 of Table 115 is the same as compound 1 of Table 1,compound 663 of Table 115 is the same as compound 1 of Table 2, etc.)except that in all of the compounds of Table 115 Y is CBr instead of CH.

Table 116

Table 116 consists of 6620 compounds. Each of these compounds is exactlythe same as the corresponding compound in Tables 1 to 10 (thus, forexample, compound 1 of Table 116 is the same as compound 1 of Table 1,compound 663 of Table 116 is the same as compound 1 of Table 2, etc.)except that in all of the compounds of Table 116 Y is CCH₃ instead ofCH.

Table 117

Table 117 consists of 662 compounds of the general formula (1B), where Wand Z are CH and X and Y are N, R is Cl, R¹ is 2,4,6-trifluorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 117 is the same as compound 1 of Table 21 except that incompound 1 of Table 117, the compound has the general formula (1B).Similarly, compounds 2 to 662 of Table 117 are the same as compounds 2to 662 of Table 21 except that in the compounds of Table 117, thecompounds have the general formula (1B).

Table 118

Table 118 consists of 662 compounds of the general formula (1B), where Wand Z are CH and X and Y are N, R is Cl, R¹ is 2,5,6-trifluorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 118 is the same as compound 1 of Table 22 except that incompound 1 of Table 118, the compound has the general formula (1B).Similarly, compounds 2 to 662 of Table 118 are the same as compounds 2to 662 of Table 22 except that in the compounds of Table 118, thecompounds have the general formula (1B).

Table 119

Table 119 consists of 662 compounds of the general formula (1B), where Wand Z are CH and X and Y are N, R is Cl, R¹ is2,3,4,5,6-pentafluorophenyl, and the values of R³ and R⁴ are as listedin Table 1. Thus, compound 1 of Table 119 is the same as compound 1 ofTable 23 except that in compound 1 of Table 119, the compound has thegeneral formula (1B). Similarly, compounds 2 to 662 of Table 119 are thesame as compounds 2 to 662 of Table 23 except that in the compounds ofTable 119, the compounds have the general formula (1B).

Table 120

Table 120 consists of 662 compounds of the general formula (1B), where Wand Z are CH and X and Y are N, R is Cl, R¹ is2,6-difluoro-4-methoxyphenyl, and the values of R³ and R⁴ are as listedin Table 1. Thus, compound 1 of Table 120 is the same as compound 1 ofTable 24 except that in compound 1 of Table 120, the compound has thegeneral formula (1B). Similarly, compounds 2 to 662 of Table 120 are thesame as compounds 2 to 662 of Table 24 except that in the compounds ofTable 120, the compounds have the general formula (1B).

Table 121

Table 121 consists of 662 compounds of the general formula (1B), where Wand Z are CH and X and Y are N, R is Cl, R¹ is 2-fluoro-6-chlorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 121 is the same as compound 1 of Table 25 except that incompound 1 of Table 121, the compound has the general formula (1B).Similarly, compounds 2 to 662 of Table 121 are the same as compounds 2to 662 of Table 25 except that in the compounds of Table 121, thecompounds have the general formula (1B).

Table 122

Table 122 consists of 662 compounds of the general formula (1B), where Wand X are CH and Y and Z are N, R is Cl, R¹ is 2,4,6-trifluorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 122 is the same as compound 1 of Table 26 except that incompound 1 of Table 122, the compound has the general formula (1B).Similarly, compounds 2 to 662 of Table 122 are the same as compounds 2to 662 of Table 26 except that in the compounds of Table 122, thecompounds have the general formula (1B).

Table 123

Table 123 consists of 662 compounds of the general formula (1B), where Wand X are CH and Y and Z are N, R is Cl, R¹ is 2,4,5-trifluorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 123 is the same as compound 1 of Table 27 except that incompound 1 of Table 123, the compound has the general formula (1B).Similarly, compounds 2 to 662 of Table 123 are the same as compounds 2to 662 of Table 27 except that in the compounds of Table 123, thecompounds have the general formula (1B).

Table 124

Table 124 consists of 662 compounds of the general formula (1B), where Wand X are CH and Y and Z are N, R is Cl, R¹ is2,3,4,5,6-pentafluorophenyl, and the values of R³ and R⁴ are as listedin Table 1. Thus, compound 1 of Table 124 is the same as compound 1 ofTable 28 except that in compound 1 of Table 124, the compound has thegeneral formula (1B). Similarly, compounds 2 to 662 of Table 124 are thesame as compounds 2 to 662 of Table 28 except that in the compounds ofTable 124, the compounds have the general formula (1B).

Table 125

Table 125 consists of 662 compounds of the general formula (1B), where Wand X are CH and Y and Z are N, R is Cl, R¹ is2,6-difluoro-4-methoxyphenyl, and the values of R³ and R⁴ are as listedin Table 1. Thus, compound 1 of Table 125 is the same as compound 1 ofTable 29 except that in compound 1 of Table 125, the compound has thegeneral formula (1B). Similarly, compounds 2 to 662 of Table 125 are thesame as compounds 2 to 662 of Table 29 except that in the compounds ofTable 125, the compounds have the general formula (1B).

Table 126

Table 126 consists of 662 compounds of the general formula (1B), where Wand X are CHI and Y and Z are N, R is Cl, R¹ is 2-fluoro-6-chlorophenyl,and the values of R³ and R⁴ are as listed in Table 1. Thus, compound 1of Table 126 is the same as compound 1 of Table 30 except that incompound 1 of Table 126, the compound has the general formula (1B).Similarly, compounds 2 to 662 of Table 126 are the same as compounds 2to 662 of Table 30 except that in the compounds of Table 126, thecompounds have the general formula (11B).

Table 127

Table 127 consists of 662 compounds of the general formula (1A), where Wand Z are N and X and Y are CH, R is NR³R⁴, R¹ is 2,4,6-trifluorophenyland the values of R³ and R⁴ are listed in Table 1. Thus, compound 1 ofTable 127 is the same as compound 1 of Table 1 except that in compound 1of Table 127, R is NR³R⁴. Similarly, compounds 2 to 662 of Table 127 arethe same as compounds 2 to 662 of Table 1 except that in the compoundsof Table 127, R is NR³R⁴. It should be noted that in each compound thereare the two NR³R⁴ groups, both of which are the same. In other words R³and R⁴ in the NR³R⁴ group shown in formula (1A) and in the NR³R⁴ groupthat is R, have the same values. These are the values set out in Table1.

Compounds of formula (7) or (8), which are examples of compounds ofgeneral formula (1) where one of R and R² is NR³R⁴, can be made as shownin Scheme 1, in which W, X, Y, Z, R¹, R³ and R⁴ have the meanings givenabove and R⁷ is C₁₋₄ alkyl.

Compounds of general formula (4) can be prepared from compounds ofgeneral formula (2), which are either commercially available or made bymethods known in the literature, by reaction with acids of generalformula (3), using standard coupling methods, for example by conversionto the acid chloride using a chlorinating agent such as thionylchloride, followed by reaction of the resultant acid chloride optionallyin the presence of a base such as triethylamine, in a suitable solventsuch as dichloromethane or toluene. Compounds of general formula (5) canbe prepared by treating compounds of general formula (4) with a basesuch as sodium hydride, optionally in the presence of a Lewis acid suchas magnesium oxide, in a suitable solvent such as N,N-dimethylformamide(DMF) or toluene, at between room temperature and 150° C., butpreferably at 60-90° C. Compounds of general formula (6) can be preparedby reaction of compounds of general formula (5) with a chlorinationreagent such as phosphorus oxychloride, either neat or in a suitablesolvent such as toluene, at between 50 and 150° C., but preferablybetween 80 and 110° C., or in a microwave reactor at between 150 and300° C., but preferably between 200 and 250° C. Compounds of formula (7)and (8) can be prepared by reaction of compounds of general formula (6)with an amine R³R⁴NH, either neat, or in a suitable solvent such as DMF,between room temperature and 150° C., but preferably between 50 and 80°C. If compounds (7) and (8) are produced as a mixture they can beseparated by suitable means such as crystallisation or chromatographyunder normal or reverse phase conditions.

Compounds of the general formulae (5), (6), (7) and (8) may bederivatised, via the chloro or hydroxy substituents, using routinechemical techniques to form other compounds of the general formula (1).Alternatively, other compounds of the general formula (1) may beprepared using a similar methodology to that described for preparing thecompounds (5) to (8) and employing preparative techniques known from thechemical literature.

Compounds of formula (7) can also be made as shown in scheme 2.

Compounds of general formula (10) can be prepared from compounds ofgeneral formula (9), which are either commercially available or made bymethods known in the literature, by reaction with acids of generalformula (3), using standard coupling methods, for example by conversionto the acid chloride using a chlorinating agent such as thionylchloride, followed by reaction of the resultant acid chloride optionallyin the presence of a base such as triethylamine, in a suitable solventsuch as dichloromethane or toluene. Compounds of general formula (11)can be prepared by treating compounds of general formula (10) with abase such as sodium hydride, optionally in the presence of a Lewis acidsuch as magnesium oxide, in a suitable solvent such asN,N-dimethylformamide (DMF) or toluene, at between room temperature and150° C., but preferably at 60-90° C. Compounds of general formula (12)can be prepared by reaction of compounds of general formula (11) with achlorination reagent such as phosphorus oxychloride, either neat or in asuitable solvent such as toluene, at between 50 and 150° C., butpreferably between 80 and 110° C., or in a microwave reactor at between150 and 300° C., but preferably between 200 and 250° C. Compounds offormula (7) can be prepared from compounds of formula (12) by reductiveamination, for example by reaction with a ketone or aldehyde in asuitable solvent such as ethanol or toluene, at between room temperatureand reflux, optionally in the presence of an acid catalyst such aspara-toluenesulphonic acid or a drying agent such as molecular sieves,followed by treatment with a suitable reducing agent such as sodiumborohydride, at between −20° C. and 40° C., but preferably at roomtemperature. The aldehyde or ketone is chosen so that the desired groupsR³ and R⁴ are formed after reduction of the product of reaction with theamine (12). For example if compounds of formula (12) are reacted withone equivalent of propionaldehyde and then sodium borohydride, compoundsof formula (7) where R³ is n-propyl, and R⁴ is hydrogen are formed. Ifrequired, the reaction can be repeated with a different aldehyde orketone. For example, if acetone is used for the second reaction, thencompounds of formula (7) where R³ is n-propyl and R⁴ is iso-propyl, areformed. Alternatively compounds of formula (7) can be formed fromcompounds of formula (12) by alkylation with a group R³LG, by treatmentwith a suitable base such as sodium hydride in a solvent such as DMF, ora base such as potassium carbonate in a solvent such as acetone or DMF,at between −78° C. and 100° C., but preferably between room temperatureand 60° C., followed by treatment with R⁴LG in a second step under thesame conditions if required.

Compounds of formula (13) can be prepared as shown in Scheme 3 fromcompounds of formula (6) by reaction with a source of fluoride ion, suchas potassium fluoride, in a suitable solvent such as sulpholane, at atemperature between 50° C. and 200° C., but preferably at 80-150° C.Compounds of formula (14) and/or compounds of formula (15) can beprepared from difluoro compounds of formula (13) by reaction with anamine of formula R³R⁴NH in a suitable solvent such as DMF or CH₂Cl₂, ata temperature of 0° C.-100° C., but preferably at room temperature.

Compounds of general formula (16), where Hall is chlorine or fluorine,can be converted into compounds of formula (17), (18), (19), (20), (21),(22) or (23) as shown in Scheme 4. Compounds of general formula (17)where Hal² is bromine or iodine can be formed by reacting compounds ofgeneral formula (16) with a metal halide, for example cuprous bromide,in a suitable solvent, for example DMF, at between room temperature and155° C., but preferably between 70° C. and 155° C. Compounds of generalformula (18) where V is oxygen or sulphur and R⁹ is C₁₋₈ alkyl, can beformed by reacting compounds of general formula (16) with a metalalkoxide or thioalkoxide MVR⁹ in a suitable solvent, for example sodiummethoxide in methanol, at room temperature to 65° C. Compounds ofgeneral formula (19) can be formed by reacting compounds of generalformula (16) with a metal cyanide in a suitable solvent, for examplecuprous cyanide in DMF, at between room temperature and 155° C. butpreferably between 50° C. and 155° C. Compounds of general formula (20)where R¹⁰ is C₁₋₈ alkyl, can be formed by reacting compounds of generalformula (16) with an alkyl metal derivative in a suitable solvent, forexample methyl magnesium bromide in THF, optionally in the presence ofcatalyst such as cuprous bromide or Pd(Ph)₄, between 40° C. and 50° C.Compounds of general formula (21) can be formed by reduction ofcompounds of general formula (16), where Hal¹ is chlorine, for exampleby hydrogenolysis with hydrogen gas and a metal catalyst such aspalladium on carbon in a suitable solvent such as ethanol, at roomtemperature. Compounds of general formula (22) where R¹¹ is hydrogen orC₁₋₆ alkyl, can be formed by reaction of compounds of general formula(16) with an alkyl acetylene under the Sonogashira conditions, forexample with 1-propyne in triethylamine in the presence of a cuproussalt such as cuprous iodide and a palladium catalyst such as Pd(Ph)₄,between room temperature and 70° C. Compounds of general formula (23)where R¹² is hydrogen or C₁₋₆ alkyl, can be formed by reaction ofcompounds of general formula (16) with an alkenyl metal derivative in asuitable solvent, such as ethenylboronic acid in THF, in the presence ofa palladium catalyst such as Pd(Ph)₄ and a base such as caesiumcarbonate, between room temperature and 65° C.

In Scheme 5 compounds of general formula (24), where the two R³R⁴Ngroups are identical, can be made from compounds of general formula (13)by reaction with a large excess of amine R³R⁴NH in a suitable solventsuch as DMF, at a temperature between 0° C. and 150° C., but preferablybetween room temperature and 100° C.

Further assistance in the preparation of the compounds of formula (1)may be derived from the following publications: Emilio, Toja, et. al.,J. Heterocyclic Chem., 23, 1955 (1986), H. Schäfer, et. al., J. f.prakt. Chemie, 321(4), 695 (1970) and H. Bredereck et. al., Chem Ber.96, 1868-1872 (1993).

The intermediate chemicals having the general formulae (4), (5), (6) and(13):

wherein W, X, Y, Z, R¹ and R⁷ are as define above, are believed to benovel compounds and form a further part of this invention.

It should be noted that the intermediate of general formula (5) mayexist in the tautomeric forms (a), (b) and (c) as well as in the formshown in formula (5):

The invention as defined by the general formula (5) embraces all suchtautomers.

Of particular interest are the intermediates listed in Tables 128 to 132below. In Table 128 the compounds have the general formula (4) where R⁷is methyl and W, X, Y, Z and R¹ have the values shown in the table.TABLE 128 Cmpd No. R¹ W X Y Z 1 2,4,6-trifluorophenyl N CH CH N 22,5,6-trifluorophenyl N CH CH N 3 2,3,4,5,6-pentafluorophenyl N CH CH N4 2,3,5,6-tetrafluorophenyl N CH CH N 5 2,6-difluoro-4-methoxyphenyl NCH CH N 6 2-fluoro-6-chlorophenyl N CH CH N 7 2,6-difluorophenyl N CH CHN 8 2,3,5,6-tetrafluorophenyl N CH CH N 9 2-fluorophenyl N CH CH N 102-chlorophenyl N CH CH N 11 2-bromophenyl N CH CH N 122,4-dichlorophenyl N CH CH N 13 2,4,6-trifluorophenyl N N CH CH 142,5,6-trifluorophenyl N N CH CH 15 2,3,4,5,6-pentafluorophenyl N N CH CH16 2,3,5,6-tetrafluorophenyl N N CH CH 17 2,6-difluoro-4-methoxyphenyl NN CH CH 18 2-fluoro-6-chlorophenyl N N CH CH 19 2,6-difluorophenyl N NCH CH 20 2,3,5,6-tetrafluorophenyl N N CH CH 21 2-fluorophenyl N N CH CH22 2-chlorophenyl N N CH CH 23 2-bromophenyl N N CH CH 242,4-dichlorophenyl N N CH CH 25 2,4,6-trifluorophenyl CH N N CH 262,5,6-trifluorophenyl CH N N CH 27 2,3,4,5,6-pentafluorophenyl CH N N CH28 2,3,5,6-tetrafluorophenyl CH N N CH 29 2,6-difluoro-4-methoxyphenylCH N N CH 30 2-fluoro-6-chlorophenyl CH N N CH 31 2,6-difluorophenyl CHN N CH 32 2,3,5,6-tetrafluorophenyl CH N N CH 33 2-fluorophenyl CH N NCH 34 2-chlorophenyl CH N N CH 35 2-bromophenyl CH N N CH 362,4-dichlorophenyl CH N N CH 37 2,4,6-trifluorophenyl CH CH N N 382,5,6-trifluorophenyl CH CH N N 39 2,3,4,5,6-pentafluorophenyl CH CH N N40 2,3,5,6-tetrafluorophenyl CH CH N N 41 2,6-difluoro-4-methoxyphenylCH CH N N 42 2-fluoro-6-chlorophenyl CH CH N N 43 2,6-difluorophenyl CHCH N N 44 2,3,5,6-tetrafluorophenyl CH CH N N 45 2-fluorophenyl CH CH NN 46 2-chlorophenyl CH CH N N 47 2-bromophenyl CH CH N N 482,4-dichlorophenyl CH CH N NTable 129

Table 129 consists of 48 compounds of the general formula (5), where W,X, Y, Z and R¹ have the values given in Table 128. Thus, compound 1 ofTable 129 has the same W, X, Y, Z and R¹ values as compound 1 of Table128, etc.

Table 130

Table 130 consists of 48 compounds of the general formula (6), where W,X, Y, Z and R¹ have the values given in Table 128. Thus, compound 1 ofTable 130 has the same W, X, Y, Z and R¹ values as compound 1 of Table128, etc.

Table 131

Table 131 consists of 48 compounds of the general formula (13), where W,X, Y, Z and R¹ have the values given in Table 128. Thus, compound 1 ofTable 131 has the same W, X, Y, Z and R¹ values as compound 1 of Table128, etc.

Table 132

Table 132 consists of 48 compounds of the general formula (4), where W,X, Y, Z and R¹ have the values given in Table 128 and R⁷ is ethyl. Thus,compound 1 of Table 132 is the same as compound 1 of Table 128 exceptthat in compound 1 of Table 132, R⁷ is ethyl instead of methyl.Similarly, compounds 2 to 48 of Table 132 are the same as compounds 2 to48 of Table 128 except that in the compounds of Table 132, R⁷ is ethyl.

The compounds of formula (1) are active fungicides and may be used tocontrol one or more of the following pathogens: Pyricularia oryzae(Magnaporthe grisea) on rice and wheat and other Pyricularia spp. onother hosts; Puccinia triticina (or recondita), Puccinia striiformis andother rusts on wheat, Puccinia hordei, Puccinia striiformis and otherrusts on barley, and rusts on other hosts (for example turf, rye,coffee, pears, apples, peanuts, sugar beet, vegetables and ornamentalplants); Erysiphe cichoracearum on cucurbits (for example melon);Blumeria (or Erysiphe) graminis (powdery mildew) on barley, wheat, ryeand turf and other powdery mildews on various hosts, such asSphaerotheca macularis on hops, Sphaerotheca fusca (Sphaerothecafuliginea) on cucurbits (for example cucumber), Leveillula taurica ontomatoes, aubergine and green pepper, Podosphaera leucotricha on applesand Uncinula necator on vines; Cochliobolus spp., Helminthosporium spp.,Drechslera spp. (Pyrenophora spp.), Rhynchosporium spp., Mycosphaerellagraminicola (Septoria tritici) and Phaeosphaeria nodorum (Stagonosporanodorum or Septoria nodorum), Pseudocercosporella herpotrichoides andGaeumannomyces graminis on cereals (for example wheat, barley, rye),turf and other hosts; Cercospora arachidicola and Cercosporidiumpersonatum on peanuts and other Cercospora spp. on other hosts, forexample sugar beet, bananas, soya beans and rice; Botrytis cinerea (greymould) on tomatoes, strawberries, vegetables, vines and other hosts andother Botrytis spp. on other hosts; Alternaria spp. on vegetables (forexample carrots), oil-seed rape, apples, tomatoes, potatoes, cereals(for example wheat) and other hosts; Venturia spp. (including Venturiainaequalis (scab)) on apples, pears, stone fruit, tree nuts and otherhosts; Cladosporium spp. on a range of hosts including cereals (forexample wheat) and tomatoes; Monilinia spp. on stone fruit, tree nutsand other hosts; Didymella spp. on tomatoes, turf, wheat, cucurbits andother hosts; Phoma spp. on oil-seed rape, turf, rice, potatoes, wheatand other hosts; Aspergillus spp. and Aureobasidium spp. on wheat,lumber and other hosts; Ascochyta spp. on peas, wheat, barley and otherhosts; Stemphylium spp. (Pleospora spp.) on apples, pears, onions andother hosts; summer diseases (for example bitter rot (Glomerellacingulata), black rot or frogeye leaf spot (Botryosphaeria obtusa),Brooks fruit spot (Mycosphaerella pomi), Cedar apple rust(Gymnosporangium juniperi-virginianae), sooty blotch (Gloeodespomigena), flyspeck (Schizothyrium pomi) and white rot (Botryosphaeriadothidea)) on apples and pears; Plasmopara viticola on vines; otherdowny mildews, such as Bremia lactucae on lettuce, Peronospora spp. onsoybeans, tobacco, onions and other hosts, Pseudoperonospora humuli onhops and Pseudoperonospora cubensis on cucurbits; Pythium spp.(including Pythium ultimum) on turf and other hosts; Phytophthorainfestans on potatoes and tomatoes and other Phytophdzora spp. onvegetables, strawberries, avocado, pepper, ornamentals, tobacco, cocoaand other hosts; Thanatephorus cucumeris on rice and turf and otherRhizoctonia spp. on various hosts such as wheat and barley, peanuts,vegetables, cotton and turf; Sclerotinia spp. on turf, peanuts,potatoes, oil-seed rape and other hosts; Sclerotium spp. on turf,peanuts and other hosts; Gibberella fujikuroi on rice; Colletotrichumspp. on a range of hosts including turf, coffee and vegetables;Laetisaria fuciformis on turf; Mycosphaerella spp. on bananas, peanuts,citrus, pecans, papaya and other hosts; Diaporthe spp. on citrus,soybean, melon, pears, lupin and other hosts; Elsinoe spp. on citrus,vines, olives, pecans, roses and other hosts; Verticillium spp. on arange of hosts including hops, potatoes and tomatoes; Pyrenopeziza spp.on oil-seed rape and other hosts; Oncobasidium theobromae on cocoacausing vascular streak dieback; Fusarium spp., Typhula spp.,Microdochium nivale, Ustilago spp., Urocystis spp., Tilletia spp. andClaviceps purpurea on a variety of hosts but particularly wheat, barley,turf and maize; Ramularia spp. on sugar beet, barley and other hosts;post-harvest diseases particularly of fruit (for example Penicilliuindigitatum, Penicilliuyn italicum and Trichoderma viride on oranges,Colletotrichum musae and Gloeosporium musarum on bananas and Botrytiscinerea on grapes); other pathogens on vines, notably Eutypa lata,Guignardia bidwellii, Phellinus igniarus, Phoinopsis viticola,Pseudopeziza tracheiphila and Stereum hirsutum; other pathogens on trees(for example Lophodernium seditiosum) or lumber, notably Cephaloascusfragrans, Ceratocystis spp., Ophiostoma piceae, Penicillium spp.,Trichoderma pseudokoningii, Trichoderina viride, Trichoderma harzianum,Aspergillus niger, Leptographium lindbergi and Aureobasidium pullulans;and fungal vectors of viral diseases (for example Polymyxa graminis oncereals as the vector of barley yellow mosaic virus (BYMV) and Polymyxabetae on sugar beet as the vector of rhizomania).

A compound of formula (1) may move acropetally, basipetally or locallyin plant tissue to be active against one or more fungi. Moreover, acompound of formula (1) may be volatile enough to be active in thevapour phase against one or more fingi on the plant.

The invention therefore provides a method of combating or controllingphytopathogenic fungi which comprises applying a fungicidally effectiveamount of a compound of formula (1), or a composition containing acompound of formula (1), to a plant, to a seed of a plant, to the locusof the plant or seed or to soil or any other plant growth medium, e.g.nutrient solution.

The term “plant” as used herein includes seedlings, bushes and trees.Furthermore, the fungicidal method of the invention includes protectant,curative, systemic, eradicant and antisporulant treatments.

The compounds of formula (1) are preferably used for agricultural,horticultural and turfgrass purposes in the form of a composition.

In order to apply a compound of formula (1) to a plant, to a seed of aplant, to the locus of the plant or seed or to soil or any other growthmedium, a compound of formula (1) is usually formulated into acomposition which includes, in addition to the compound of formula (1),a suitable inert diluent or carrier and, optionally, a surface activeagent (SFA). SFAs are chemicals that are able to modify the propertiesof an interface (for example, liquid/solid, liquid/air or liquid/liquidinterfaces) by lowering the interfacial tension and thereby leading tochanges in other properties (for example dispersion, emulsification andwetting). It is preferred that all compositions (both solid and liquidformulations) comprise, by weight, 0.0001 to 95%, more preferably 1 to85%, for example 5 to 60%, of a compound of formula (1). The compositionis generally used for the control of fuigi such that a compound offormula (1) is applied at a rate of from 0.1 g to 10 kg per hectare,preferably from 1 g to 6 kg per hectare, more preferably from 1 g to 1kg per hectare.

When used in a seed dressing, a compound of formula (1) is used at arate of 0.0001 g to 10 g (for example 0.001 g or 0.05 g), preferably0.005 g to 10 g, more preferably 0.005 g to 4 g, per kilogram of seed.

In another aspect the present invention provides a fungicidalcomposition comprising a fungicidally effective amount of a compound offormula (1) and a suitable carrier or diluent therefor.

In a still further aspect the invention provides a method of combatingand controlling fungi at a locus, which comprises treating the fungi, orthe locus of the fungi with a fungicidally effective amount of acomposition comprising a compound of formula (1).

The compositions can be chosen from a number of formulation types,including dustable powders (DP), soluble powders (SP), water solublegranules (SG), water dispersible granules (WG), wettable powders (WP),granules (GR) (slow or fast release), soluble concentrates (SL), oilmiscible liquids (OL), ultra low volume liquids (UL), emulsifiableconcentrates (EC), dispersible concentrates (DC), emulsions (both oil inwater (EW) and water in oil (BO)), micro-emulsions (ME), suspensionconcentrates (SC), aerosols, fogging/smoke formulations, capsulesuspensions (CS) and seed treatment formulations. The formulation typechosen in any instance will depend upon the particular purpose envisagedand the physical, chemical and biological properties of the compound offormula (1).

Dustable powders (DP) may be prepared by mixing a compound of formula(1) with one or more solid diluents (for example natural clays, kaolin,pyrophyllite, bentonite, alumina, montmnorillonite, kieselguhr, chalk,diatomaceous earths, calcium phosphates, calcium and magnesiumcarbonates, sulphur, lime, flours, talc and other organic and inorganicsolid carriers) and mechanically grinding the mixture to a fine powder.

Soluble powders (SP) may be prepared by mixing a compound of formula (1)with one or more water-soluble inorganic salts (such as sodiumbicarbonate, sodium carbonate or magnesium sulphate) or one or morewater-soluble organic solids (such as a polysaccharide) and, optionally,one or more wetting agents, one or more dispersing agents or a mixtureof said agents to improve water dispersibility/solubility. The mixtureis then ground to a fine powder. Similar compositions may also begranulated to form water soluble granules (SG).

Wettable powders (WP) may be prepared by mixing a compound of formula(1) with one or more solid diluents or carriers, one or more wettingagents and, preferably, one or more dispersing agents and, optionally,one or more suspending agents to facilitate the dispersion in liquids.The mixture is then ground to a fine powder. Similar compositions mayalso be granulated to form water dispersible granules (WG).

Granules (GR) may be formed either by granulating a mixture of acompound of formula (1) and one or more powdered solid diluents orcarriers, or from pre-formed blank granules by absorbing a compound offormula (1) (or a solution thereof, in a suitable agent) in a porousgranular material (such as pumice, attapulgite clays, fuller's earth,kieselguhr, diatomaceous earths or ground corn cobs) or by adsorbing acompound of formula (1) (or a solution thereof, in a suitable agent) onto a hard core material (such as sands, silicates, mineral carbonates,sulphates or phosphates) and drying if necessary. Agents which arecommonly used to aid absorption or adsorption include solvents (such asaliphatic and aromatic petroleum solvents, alcohols, ethers, ketones andesters) and sticking agents (such as polyvinyl acetates, polyvinylalcohols, dextrins, sugars and vegetable oils). One or more otheradditives may also be included in granules (for example an emulsifyingagent, wetting agent or dispersing agent).

Dispersible Concentrates (DC) may be prepared by dissolving a compoundof formula (1) in water or an organic solvent, such as a ketone, alcoholor glycol ether. These solutions may contain a surface active agent (forexample to improve water dilution or prevent crystallisation in a spraytank).

Emulsifiable concentrates (EC) or oil-in-water emulsions (EW) may beprepared by dissolving a compound of formula (1) in an organic solvent(optionally containing one or more wetting agents, one or moreemulsifying agents or a mixture of said agents). Suitable organicsolvents for use in ECs include aromatic hydrocarbons (such asalkylbenzenes or alkylnaphthalenes, exemplified by SOLVESSO 100,SOLVESSO 150 and SOLVESSO 200; SOLVESSO is a Registered Trade Mark),ketones (such as cyclohexanone or methylcyclohexanone), alcohols (suchas benzyl alcohol, furfuryl alcohol or butanol), N-alkylpyrrolidones(such as N-methylpyrrolidone or N-octylpyrrolidone), dimethyl amides offatty acids (such as C₈-C₁₀ fatty acid dimethylamide) and chlorinatedhydrocarbons. An EC product may spontaneously emulsify on addition towater, to produce an emulsion with sufficient stability to allow sprayapplication through appropriate equipment. Preparation of an EW involvesobtaining a compound of formula (1) either as a liquid (if it is not aliquid at room temperature, it may be melted at a reasonabletemperature, typically below 70° C.) or in solution (by dissolving it inan appropriate solvent) and then emulsifying the resultant liquid orsolution into water containing one or more SFAs, under high shear, toproduce an emulsion. Suitable solvents for use in EWs include vegetableoils, chlorinated hydrocarbons (such as chlorobenzenes), aromaticsolvents (such as alkylbenzenes or alkylnaphthalenes) and otherappropriate organic solvents that have a low solubility in water.

Microemulsions (ME) may be prepared by mixing water with a blend of oneor more solvents with one or more SFAs, to produce spontaneously athermodynamically stable isotropic liquid formulation. A compound offormula (1) is present initially in either the water or the solvent/SFAblend. Suitable solvents for use in MEs include those hereinbeforedescribed for use in in ECs or in EWs. An ME may be either anoil-in-water or a water-in-oil system (which system is present may bedetermined by conductivity measurements) and may be suitable for mixingwater-soluble and oil-soluble pesticides in the same formulation. An MEis suitable for dilution into water, either remaining as a microemulsionor forming a conventional oil-in-water emulsion.

Suspension concentrates (SC) may comprise aqueous or non-aqueoussuspensions of finely divided insoluble solid particles of a compound offormula (1). SCs may be prepared by ball or bead milling the solidcompound of formula (1) in a suitable medium, optionally with one ormore dispersing agents, to produce a fine particle suspension of thecompound. One or more wetting agents may be included in the compositionand a suspending agent may be included to reduce the rate at which theparticles settle. Alternatively, a compound of formula (1) may be drymilled and added to water, containing agents hereinbefore described, toproduce the desired end product.

Aerosol formulations comprise a compound of formula (1) and a suitablepropellant (for example n-butane). A compound of formula (1) may also bedissolved or dispersed in a suitable medium (for example water or awater miscible liquid, such as n-propanol) to provide compositions foruse in non-pressurised, hand-actuated spray pumps.

A compound of formula (1) may be mixed in the dry state with apyrotechnic mixture to form a composition suitable for generating, in anenclosed space, a smoke containing the compound.

Capsule suspensions (CS) may be prepared in a manner similar to thepreparation of EW formulations but with an additional polymerisationstage such that an aqueous dispersion of oil droplets is obtained, inwhich each oil droplet is encapsulated by a polymeric shell and containsa compound of formula (1) and, optionally, a carrier or diluenttherefor. The polymeric shell may be produced by either an interfacialpolycondensation reaction or by a coacervation procedure. Thecompositions may provide for controlled release of the compound offormula (1) and they may be used for seed treatment. A compound offormula (1) may also be formulated in a biodegradable polymeric matrixto provide a slow, controlled release of the compound.

A composition may include one or more additives to improve thebiological performance of the composition (for example by improvingwetting, retention or distribution on surfaces; resistance to rain ontreated surfaces; or uptake or mobility of a compound of formula (1)).Such additives include surface active agents, spray additives based onoils, for example certain mineral oils or natural plant oils (such assoy bean and rape seed oil), and blends of these with otherbio-enhancing adjuvants (ingredients which may aid or modify the actionof a compound of formula (1)).

A compound of formula (1) may also be formulated for use as a seedtreatment, for example as a powder composition, including a powder fordry seed treatment (DS), a water soluble powder (SS) or a waterdispersible powder for slurry treatment (WS), or as a liquidcomposition, including a flowable concentrate (FS), a solution (LS) or acapsule suspension (CS). The preparations of DS, SS, WS, FS and LScompositions are very similar to those of, respectively, DP, SP, WP, SCand DC compositions described above. Compositions for treating seed mayinclude an agent for assisting the adhesion of the composition to theseed (for example a mineral oil or a film-forming barrier).

Wetting agents, dispersing agents and emulsifying agents may be SFAs ofthe cationic, anionic, amphoteric or non-ionic type.

Suitable SFAs of the cationic type include quaternary ammonium compounds(for example cetyltrimethyl ammonium bromide), imidazolines and aminesalts.

Suitable anionic SFAs include alkali metals salts of fatty acids, saltsof aliphatic monoesters of sulphuric acid (for example sodium laurylsulphate), salts of sulphonated aromatic compounds (for example sodiumdodecylbenzenesulphonate, calcium dodecylbenzenesulphonate,butylnaphthalene sulphonate and mixtures of sodium di-isopropyl- andtri-isopropyl-naphthalene sulphonates), ether sulphates, alcohol ethersulphates (for example sodium laureth-3-sulphate), ether carboxylates(for example sodium laureth-3-carboxylate), phosphate esters (productsfrom the reaction between one or more fatty alcohols and phosphoric acid(predominately mono-esters) or phosphorus pentoxide (predominatelydi-esters), for example the reaction between lauryl alcohol andtetraphosphoric acid; additionally these products may be ethoxylated),sulphosuccinamates, paraffin or olefine sulphonates, taurates andlignosulphonates.

Suitable SFAs of the amphoteric type include betaines, propionates andglycinates.

Suitable SFAs of the non-ionic type include condensation products ofalkylene oxides, such as ethylene oxide, propylene oxide, butylene oxideor mixtures thereof, with fatty alcohols (such as oleyl alcohol or cetylalcohol) or with alkylphenols (such as octylphenol, nonylphenol oroctylcresol); partial esters derived from long chain fatty acids orhexitol anhydrides; condensation products of said partial esters withethylene oxide; block polymers (comprising ethylene oxide and propyleneoxide); alkanolamides; simple esters (for example fatty acidpolyethylene glycol esters); amine oxides (for example lauryl dimethylamine oxide); and lecithins.

Suitable suspending agents include hydrophilic colloids (such aspolysaccharides, polyvinylpyrrolidone or sodium carboxymethylcellulose)and swelling clays (such as bentonite or attapulgite).

A compound of formula (1) may be applied by any of the known means ofapplying fungicidal compounds. For example, it may be applied,formulated or unformulated, to any part of the plant, including thefoliage, stems, branches or roots, to the seed before it is planted orto other media in which plants are growing or are to be planted (such assoil surrounding the roots, the soil generally, paddy water orhydroponic culture systems), directly or it may be sprayed on, dustedon, applied by dipping, applied as a cream or paste formulation, appliedas a vapour or applied through distribution or incorporation of acomposition (such as a granular composition or a composition packed in awater-soluble bag) in soil or an aqueous environment.

A compound of formula (1) may also be injected into plants or sprayedonto vegetation using electrodynamic spraying techniques or other lowvolume methods, or applied by land or aerial irrigation systems.

Compositions for use as aqueous preparations (aqueous solutions ordispersions) are generally supplied in the form of a concentratecontaining a high proportion of the active ingredient, the concentratebeing added to water before use. These concentrates, which may includeDCs, SCs, ECs, EWs, MEs SGs, SPs, WPs, WGs and CSs, are often requiredto withstand storage for prolonged periods and, after such storage, tobe capable of addition to water to form aqueous preparations whichremain homogeneous for a sufficient time to enable them to be applied byconventional spray equipment. Such aqueous preparations may containvarying amounts of a compound of formula (1) (for example 0.0001 to 10%,by weight) depending upon the purpose for which they are to be used.

A compound of formula (1) may be used in mixtures with fertilisers (forexample nitrogen-, potassium- or phosphorus-containing fertilisers).Suitable formulation types include granules of fertiliser. The mixturessuitably contain up to 25% by weight of the compound of formula (1).

The invention therefore also provides a fertiliser compositioncomprising a fertiliser and a compound of formula (1).

The compositions of this invention may contain other compounds havingbiological activity, for example micronutrients or compounds havingsimilar or complementary fungicidal activity or which possess plantgrowth regulating, herbicidal, insecticidal, nematicidal or acaricidalactivity.

By including another fungicide, the resulting composition may have abroader spectrum of activity or a greater level of intrinsic activitythan the compound of formula (1) alone. Further the other fungicide mayhave a synergistic effect on the fungicidal activity of the compound offormula (1).

The compound of formula (1) may be the sole active ingredient of thecomposition or it may be admixed with one or more additional activeingredients such as a pesticide, fungicide, synergist, herbicide orplant growth regulator where appropriate. An additional activeingredient may: provide a composition having a broader spectrum ofactivity or increased persistence at a locus; synergise the activity orcomplement the activity (for example by increasing the speed of effector overcoming repellency) of the compound of formula (1); or help toovercome or prevent the development of resistance to individualcomponents. The particular additional active ingredient will depend uponthe intended utility of the composition.

Examples of fungicidal compounds which may be included in thecomposition of the invention are AC 382042(N-(1-cyano-1,2-dimethylpropyl)-2-(2,4-dichlorophenoxy) propionamide),acibenzolar-S-methyl, alanycarb, aldimorph, anilazine, azaconazole,azafenidin, azoxystrobin, benalaxyl, benomyl, benthiavalicarb,biloxazol, bitertanol, blasticidin S, boscalid (new name for nicobifen),bromuconazole, bupirimate, captafol, captan, carbendazim, carbendazimchlorhydrate, carboxin, carpropamid, carvone, CGA 41396, CGA 41397,chinomethionate, chlorbenzthiazone, chlorothalonil, chlorozolinate,clozylacon, copper containing compounds such as copper oxychloride,copper oxyquinolate, copper sulphate, copper tallate, and Bordeauxmixture, cyamidazosulfamid, cyazofamid (IKF-916), cyflufenamid,cymoxanil, cyproconazole, cyprodinil, debacarb, di-2-pyridyl disulphide1,1′-dioxide, dichlofluanid, diclocymet, diclomezine, dicloran,diethofencarb, difenoconazole, difenzoquat, diflumetorim,O,O-di-iso-propyl-S-benzyl thiophosphate, dimefluazole, dimetconazole,dimethirimol, dimethomorph, dimoxystrobin, diniconazole, dinocap,dithianon, dodecyl dimethyl ammonium chloride, dodemorph, dodine,doguadine, edifenphos, epoxiconazole, ethaboxam, ethirimol, ethyl(Z)-N-benzyl-N([methyl(methylthioethylideneaminooxycarbonyl)amino]thio)-β-alaninate,etridiazole, famoxadone, fenamidone, fenarimol, fenbuconazole, fenfuram,fenhexamid, fenoxanil (AC 382042), fenpiclonil, fenpropidin,fenpropimorph, fentin acetate, fentin hydroxide, ferbam, ferimzone,fluazinam, fludioxonil, flumetover, flumorph, fluoroimide,fluoxastrobin, fluquinconazole, flusilazole, flusulfamide, flutolanil,flutriafol, folpet, fosetyl-aluminium, fuberidazole, furalaxyl,furametpyr, guazatine, hexaconazole, hydroxyisoxazole, hymexazole,imazalil, imibenconazole, iminoctadine, iminoctadine triacetate,ipconazole, iprobenfos, iprodione, iprovalicarb, isopropanyl butylcarbamate, isoprothiolane, kasugamycin, kresoxim-methyl, LY186054,LY211795, LY 248908, mancozeb, maneb, mefenoxam, mepanipyrim, mepronil,metalaxyl, metalaxyl M, metconazole, metiram, metiram-zinc,metominostrobin, metrafenone, MON65500(N-allyl-4,5-dimethyl-2-trimethylsilylthiophene-3-carboxamide),myclobutanil, NTN0301, neoasozin, nickel dimethyldithiocarbamate,nitrothale-isopropyl, nuarimol, ofurace, organomercury compounds,orysastrobin, oxadixyl, oxasulfuron, oxolinic acid, oxpoconazole,oxycarboxin, pefurazoate, penconazole, pencycuron, phenazin oxide,phosphorus acids, phthalide, picoxystrobin, polyoxin D, polyram,probenazole, prochloraz, procymidone, propamocarb, propamocarbhydrochloride, propiconazole, propineb, propionic acid, proquinazid,prothioconazole, pyraclostrobin, pyrazophos, pyrifenox, pyrimethanil,pyroquilon, pyroxyfur, pyrroInitrin, quaternary ammonium compounds,quinomethionate, quinoxyfen, quintozene, silthiofam (ON 65500),S-imazalil, simneconazole, sipconazole, sodium pentachlorophenate,spiroxamine, streptomycin, sulphur, tebuconazole, tecloftalamn,tecnazene, tetraconazole, thiabendazole, thifluzamide,2-(thiocyanomethylthio)benzothiazole, thiophanate-methyl, thiram,tiadinil, timibenconazole, tolclofos-methyl, tolylfluanid, triadimefon,triadimenol, triazbutil, triazoxide, tricyclazole, tridemorph,trifloxystrobin, triflumizole, triforine, triticonazole, validamycin A,vapam, vinclozolin, XRD-563, zineb, ziram, zoxamide and compounds of theformulae:

The compounds of formula (1) may be mixed with soil, peat or otherrooting media for the protection of plants against seed-borne,soil-borne or foliar fungal diseases.

Some mixtures may comprise active ingredients, which have significantlydifferent physical, chemical or biological properties such that they donot easily lend themselves to the same conventional formulation type. Inthese circumstances other formulation types may be prepared. Forexample, where one active ingredient is a water insoluble solid and theother a water insoluble liquid, it may nevertheless be possible todisperse each active ingredient in the same continuous aqueous phase bydispersing the solid active ingredient as a suspension (using apreparation analogous to that of an SC) but dispersing the liquid activeingredient as an emulsion (using a preparation analogous to that of anEW). The resultant composition is a suspoemulsion (SE) formulation.

The invention is illustrated by the following Examples in which thefollowing abbreviations are used:

ml=millilitres f=fine

g=grammes THF=tetrahydrofuran

ppm=parts per million DCM=dichloromethane

s=singlet DMF=N,N-dimethylformamide

d=doublet DMSO=dimethylsulphoxide

t=triplet DMAP=4-dimethylaminopyridine

q=quartet NMR=nuclear magnetic resonance

m=multiplet HPLC=high performance liquid chromatography

b=broad

EXAMPLE 1

This Example illustrates the preparation of[6-chloro-7-(2,4,6-trifluorophenyl)-pyrido[2,3-b]pyrazin-8-yl]-isopropylamine(Compound No. 3, Table 1) and[8-chloro-7-(2,4,6-trifluorophenyl)-pyrido[2,3-b]pyrazin-6-yl]-isopropylamine(Compound No. 3, Table 6).

Compound No. 3, Table 1

Compound No. 3, Table 6Step 1

Methyl 2-amino-3-pyrazine carboxylate (2.2 g) was dissolved in dry DCM(20 ml) to give a cloudy pale yellow solution, and pyridine (2 ml) indry DCM (12 ml) was added. The stirred suspension was cooled in an icebath, and 2,4,6-trifluorophenylacetyl chloride (3.0 g) in dry DCM (13ml) was added dropwise. The reaction gradually became a deep orange, andthen went clear. It was stirred for 6 hours and stood overnight. Thereaction mixture was washed with water, brine, and then dilutehydrochloric acid, and the DCM layer was dried over magnesium sulphate.The solvent was evaporated to yield an orange solid which was trituratedwith ether, to give methyl2-[2,4,6-trifluorophenylacetylamino]-3-pyrazine carboxylate as a yellowsolid (1.5 g).

¹H NMR (CDCl₃) δ ppm: 4.03 (s,5H), 6.74 (t,2H), 8.43 (d,1H), 8.61 (d,1H)10.9 (s,1H).

Step 2

The product of Step 1 (3.25 g) was dissolved in DMF (10 ml) and addeddropwise to a stirred suspension of sodium hydride (0.60 g of an 80%dispersion in mineral oil) in DMF (80 ml). There was an immediatereaction, and the mixture was stirred at room temperature for 2 hours,and at 80° C. for 8 hours. The reaction mixture was cooled andevaporated to give a yellow solid (3 g), which was then acidified withdilute hydrochloric acid. The resultant white suspension was filteredand collected, washed with ether and dried to give6,8-dihydroxy-7-(2,4,6-trifluorophenyl)pyrido[2,3-b]pyrazine (1.8 g).

¹H NMR (d⁶-DMSO) δ ppm: 7.25 (t,2H), 8.6 (fd,1H), 8.7 (fd,1H), 12.6(s,1H).

Step 3

The product from Step 2 (0.90 g) was added portion-wise to phosphorusoxychloride (10 ml) with stirring. The reaction was exothermic. Themixture became brown with a fine suspension, and was then refluxed for 6hours. Excess phosphorus oxychloride was evaporated, the mixture wasdiluted with DCM, and then washed with water to give a black oil, whichwas purified by flash column chromatography on silica gel (40-60)eluting with diethyl ether, to give6,8-dichloro-7-(2,4,6-trifluorophenyl)pyrido[2,3-b]pyrazine as a darkoil (0.40 g).

¹H NMR (CDCl₃) δ ppm: 6.9 (t,2H), 9.1 (d,1H), 9.2 (d,1H).

Alternative Procedure for Step 3

Phosphorus oxychloride (20.90 g) was added over 15 minutes to asuspension of the product from Step 2 (10.0 g), in 1,2-dichloroethane(80 ml) containing DMF (5.0 g) maintained at a temperature between79°-81° C. Stirring was continued at this temperature for 3 hours, andthe reaction was then cooled. The mixture was poured carefully intosaturated sodium bicarbonate solution (500 ml) keeping the temperaturebelow 30° C. After stirring for 20 minutes the product was extractedwith ethyl acetate, washed with water and brine and dried over sodiumsulphate. The solvent was evaporated to yield a dark red oil, which waspurified by flash chromatography eluting with cyclohexane:ethyl acetate,4:1 to give 6,8-dichloro-7-(2,4,6-trifluorophenyl)pyrido[2,3-b]pyrazineas a light brown solid (7.5 g),m.p. 139-141° C.

Step 4

The product from Step 3 (0.20 g), isopropylamine (1.0 ml) andN-ethyldiisopropylamine (0.20 g) were refluxed in a sealed tube at 90°C. for 17 hours. The dark coloured reaction mixture was evaporated togive an oil, which was purified by flash column chromatography on silicagel (40-60) in diethyl ether to give[8-chloro-7-(2,4,6-trifluorophenyl)-pyrido[2,3-b]pyrazin-6-yl]-isopropylamineas a yellow solid (0.025 g).

¹H NMR (CDCl₃) δ ppm: 1.25 (d,6H), 4.62 (bd,1H), 4.75 (m,1H), 6.67(m,2H), 8.64 (d,1H), 8.85 (d,1H).

A fraction containing a mixture of isomers (0.080 g), was also obtained,and a portion of this mixture (0.020 g) was purified by reverse phaseHPLC on a Kromasil 100-5C18 column, eluting with methanol:water (65:35)to give[6-chloro-7-(2,4,6-trifluorophenyl)-pyrido[2,3-b]pyrazin-8-yl]-isopropylamineas a frothy solid (0.013 g).

¹H NMR (CDCl₃) δ ppm: 1.1 (d,6H), 3.26 (m,1H), 6.84 (m,2H), 6.95(bd,1H), 8.67 (d,1H), 9.0 (d,1H).

EXAMPLE 2

This Example illustrates the preparation of[6-fluoro-7-(2,4,6-trifluorophenyl)pyrido[2,3-b]pyrazin-8-yl]-isopropylamine(Compound No. 3, Table 103)

Step 1

6,8-Dichloro-7-(2,4,6-trifluorophenyl)-pyrido[2,3-b]pyrazine (1.25 g)and potassium fluoride (0.66 g, spray dried) in dry sulpholane (5 ml)were heated to 130° C. for 16 hours. The reaction mixture was pouredinto water and extracted with ethyl acetate. The extract was washed withwater and brine and dried over sodium sulphate. After evaporation of thesolvent, the remaining oil was purified by flash chromatography onsilica gel eluting with cyclohexane:ethyl acetate, 3:1 to yield6,8-difluoro-7-(2,4,6-trifluorophenyl)-pyrido[2,3-b]-pyrazine as aslightly brownish solid (0.79 g), m.p. 120-121° C.

Step 2

The product from Step 1 (0.30 g) was added to a suspension ofisopropylamine (0.090 g), potassium carbonate (0.21 g) and a catalyticamount of DMAP in DMF (3 ml), and the mixture was stirred at roomtemperature for 19 hours. After addition of ethyl acetate, the mixturewas washed with water and brine, dried over sodium sulphate, filteredand the solvent evaporated. The residue was purified by flashchromatography eluting with toluene:ethyl acetate, 9:1 to give[6-fluoro-7-(2,4,6-trifluorophenyl)-pyrido[2,3-b]pyrazin-8-yl]-isopropylamineas a yellow powder (0.20 g), m.p. 127-128° C.

EXAMPLE 3

This Example illustrates the preparation of[6-chloro-7-(2,4,6-trifluorophenyl)-pyrido[3,2-c]pyridazin-8-yl]-isopropylamine(Compound No. 3, Table 11) and[8-chloro-7-(2,4,6-trifluorophenyl)-pyrido[3,2-c]pyridazin-6-yl]-isopropylamine(Compound No. 3, Table 16).

Compound No. 3, Table 11

Compound No. 3, Table 16Step 1

A solution of 4-aminopyridazine-3-carbonitrile (0.248 g, prepared as inJ. Het. Chem. (1970), 3, 467-473) in absolute ethanol (30 ml) wassaturated with hydrogen chloride gas, the flask being cooled in an icebath. The ice bath was then removed and the resulting solution wasrefluxed for 18 hours. It was then cooled, the solvent evaporated, andcold, saturated aqueous sodium bicarbonate was added. The aqueous phasewas then extracted with DCM, the organic phases were combined, driedover magnesium sulphate, filtered and evaporated to give4-aminopyridazine-3-carboxylic acid ethyl ester as a white solid (0.229g). The aqueous phase was evaporated, DCM was added, the organic phasewas isolated, dried over magnesium sulphate, filtered and evaporatedunder vacuo to give further ester as a white solid (0.010 g), m.p.149-150° C.

¹H NMR (CDCl₃) δ ppm: 1.48 (t,3H), 4.52 (q,2H), 6.73 (d,1H), 8.75(d,1H).

Step 2

A mixture of the product from Step 1 (0.239 g) and DMAP (0.175 g) in drytoluene (1 ml) was added to 2,4,6-trifluorophenylacetyl chloride (crudeproduct from reaction of 0.275 g 2,4,6-trifluorophenylacetic acid andoxalyl chloride) and a few drops of DMF in toluene (1 ml) at roomtemperature, giving a thick yellow precipitate. The stirred suspensionwas heated for 3 hours at reflux, becoming dark brown/green with a greenprecipitate. It was left to stand overnight for 18 hours. The solid wascollected and washed with diethyl ether. The dark green filtrate wasevaporated to give a dark green liquid which was purified by flashcolumn chromatography on silica gel (40-60) eluting with ethyl acetateto give4-[2-(2,4,6-trifluorophenyl)-acetylamino]-pyridazine-3-carboxylic acidethyl ester as green/yellow oil that solidified on standing (0.307 g).

¹H NMR (CDCl₃) δ ppm: 1.50 (t,3H), 3.87 (s,2H), 4.55 (q,2H), 6.77(t,2H), 8.78 (d,1H), 9.15 (d,1H), 11.20 (bs,1H).

Step 3

The product from Step 2 (0.307 g) and potassium carbonate (0.25 g) werestirred in dry DMF (10 ml) at 110° C. for 2 hours and then cooled andstood for 18 hours. The DMF was evaporated and the resulting brown solidwas triturated with diethyl ether and the organic phase decanted. Thesolid was dissolved in water then acidified with dilute hydrochloricacid to neutrality. Most of the aqueous phase was then evaporated,leading to precipitation of a black solid that was filtered, and theyellow/brown aqueous phase was evaporated to dryness, affording aresidue that was dissolved in methanol, the insoluble inorganic saltswere filtered and the organic phase was evaporated to dryness to give7-(2,4,6-trifluorophenyl)-5H-pyrido[3,2-c]pyridazine-6,8-dione as alight brown/beige solid (0.258 g).

¹H NMR (CD₃OD) δ ppm: 6.83 (2d,2H), 7.44 (d,1H), 9.00 (d,1H).

Step 4

Phosphorus oxychloride (0.048 ml) was added to the product from Step 3(0.05 g) in 1,2-dichloroethane (2 ml) containing a catalytic amount ofDMF. The suspension was stirred and refluxed for 1 hour and then stoodfor 18 hours, and then refluxed for a further hour and then allowed tocool. The excess phosphorus oxychloride was evaporated to give a brownoil, which was dissolved in DCM and washed with cold water. The organiclayer was separated and dried over magnesium sulphate, filtered andevaporated to give a brown oil, which was purified by flash columnchromatography on silica gel (40-60) eluting with diethyl ether to give6,8-dichloro-7-(2,4,6-trifluorophenyl)-pyrido[3,2-c]pyridazine as ayellow oil (0.015 g).

¹HNMR(CDCl₃) δ ppm: 6.92 (m,2H), 8.11 (d,1H), 9.71 (d,1H).

Step 5

Isopropylamine (0.5 ml) was added to the product from Step 4 (0.015 g)dissolved in DCM (1 ml) containing dimethylacetamide (0.3 ml) in asealed tube. The yellow solution became yellow/greenish. The vessel wasthen sealed and stirred at room temperature. The solvents wereevaporated and the crude residue was purified using preparative thinlayer chromatography silica gel plates eluting with ethyl acetate:hexane1:1 to give two isomers:

-   [6-Chloro-7-(2,4,6-trifluorophenyl)-pyrido[3,2-c]pyridazin-8-yl]-isopropylamine    (0.003 g).

¹H NMR (CDCl₃) δ ppm: 1.16 (d,6H), 3.41 (m,1H), 6.85 (dd,2H), 7.79(bs,1H), 7.84 (d,1H). 9.40 (d,1H).

-   [8-Chloro-7-(2,4,6-trifluorophenyl)-pyrido[3,2-c]pyridazin-6-yl]-isopropylamine    (0.005 g).

¹H NMR (CDCl₃) δ ppm: 1.24 (d,6H), 4.53 (m,1H), 4.73 (d,1H), 6.94(dd,2H), 7.67 (d,1H), 9.25 (d,1H).

EXAMPLE 4

This Example illustrates the preparation of[2-chloro-3-(2,4,6-trifluorophenyl)-pyrido[2,3-d]pyridazin-4-yl]-isopropylamine(Compound No. 3, Table 21), and[4-chloro-3-(2,4,6-trifluorophenyl)-pyrido[2,3-d]pyridazin-2-yl]-isopropylamine(Compound No. 3, Table 117)

Compound No. 3, Table 21

Compound No. 3, Table 117

Step 1

5-Aminopyridazine-4-carboxylic acid ethyl ester (1.26 g, preparedaccording to J. Het. Chem., (1968), 5, 845) was dissolved in dry toluene(125 ml) at 90° C., and DMAP (0.92 g) was added.2,4,6-Trifluorophenylacetyl chloride (1.75 g of 95% purity material) wasadded dropwise with stirring at 70° C., and a white solid precipitated.The reaction was stirred at reflux for 5 hours and then filtered hot.The filtrate was evaporated to give5-[2-(2,4,6-trifluorophenyl)-acetylamino]-pyridazine-4-carboxylic acidethyl ester as a white solid (2.6 g), m.p. 143-144° C.

¹H NMR (CDCl₃) δ ppm: 1.45 (t,3H), 3.90 (s,2H), (4.45 (q,2H), 6.75(m,2H), 9.45 (s1H), 10.60 (s,1H), 11.1 (bs,1H).

Step 2

The product from Step 1 (2.5 g) was dissolved in dry THF (50 ml) and theflask purged with nitrogen. Sodium bis-trimethylsilylamide (22.1 ml of a1M solution in THF) was added dropwise with stirring at 0° C. A yellowprecipitate appeared, and the reaction was stirred for 3 hours at 0° C.The reaction was quenched with concentrated hydrochloric acid (5 ml) at0° C. and then poured onto ice water, extracted with DCM and dried overmagnesium sulphate. The solvent was evaporated to give3-(2,4,6-trifluorophenyl)-1H-pyrido[2,3-d]pyridazine-2,4-dione as ayellow solid. Further product crystallised out of the aqueous solutionovernight, to give a total yield of 1.29 g, m.p. >300° C.

¹H NMR (d⁶-DMSO) δ ppm: 7.25 (m,2H), 9.17 (s,1H), 9.47 (s,1H), 12.30(bs,1H).

Step 3

The product from Step 2 (0.10 g) was heated to 90° C. with phosphorusoxychloride (1.6 ml) with stirring. After 1 hour a clear yellow solutionwas obtained and the excess solvent was evaporated and ice water wasadded, giving a yellow solid. This was extracted with DCM, and thesolution dried over magnesium sulphate and evaporated to give2,4-dichloro-3-(2,4,6-trifluorophenyl)-pyrido[2,3-d]pyridazine as ayellow foamy glass (0.11 g).

¹H NMR (CDCl₃) δ ppm: 6.90 (m,2H), 9.80 (s,1H), 10.0 (s, H).

Step 4

Isopropylamine (1.5 ml) was added to the product from Step 3 (0.020 g)in DCM and the tube stoppered and the reaction stirred overnight at roomtemperature. The DCM was evaporated and water added to the residue,which was then extracted with DCM. The extract was dried over magnesiumsulphate and evaporated to give an orange oil, which was purified byHPLC eluting with ethyl acetate:hexane 4:1 to give two isomers:

-   [2-Chloro-3-(2,4,6-trifluorophenyl)-pyrido[2,3-d]pyridazin-4-yl]-isopropylamine    (0.007 g)

¹H NMR (CDCl₃) δ ppm: 1.27 (d,6H), 4.05 (m,1H), 4.90 (bs,1H), 6.92(m,2H), 9.55 (s,1H), 9.90 (s,1H).

-   [4-Chloro-3-(2,4,6-trifluorophenyl)-pyrido[2,3-d]pyridazin-2-yl]-isopropylanine    (0.0055 g)

¹H NMR (CDCl₃) δ ppm: 1.25 (d,6H), 4.54 (m,1H), 4.67 (bs,1H), 6.90(m,2H), 9.40 (s,1H), 9.50 (s,1H).

EXAMPLE 5

This Example illustrates the preparation of[7-chloro-6-(2,4,6-trifluorophenyl)-pyrido[2,3-c]pyridazin-5-yl]-isopropylamine(Compound No. 3, Table 26), and[5-Chloro-6-(2,4,6-trifluoro-phenyl)-pyrido[2,3-c]pyridazin-7-yl]-isopropylamine(Compound No. 3, Table 122).

Compound No. 3, Table 26

Compound No. 3, Table 122Step 1

3-Aminopyridazine-4-carboxylic acid (1.68 g, prepared as in JOC, (1985),50, 346) was refluxed in ethanol (170 ml) with concentrated hydrochloricacid (2 ml) and p-toluene-sulphonyl chloride (0.1 g) for 55 hours. Thesolvent was evaporated and ice water added to the residue, which wasthen neutralised with solid sodium bicarbonate. The mixture wasextracted with chloroform, insoluble material filtered, the organicextract dried over magnesium sulphate and evaporated to give3-aminopyridazine-4-carboxylic acid ethyl ester (1.02 g) as a whitesolid.

¹H NMR (CDCl₃) δ ppm: 1.40 (t,3H), 4.40 (q,2H), 6.50 (bs,2H), 7.74(d,1H), 8.72 (d,1H).

Step 2

The product from Step 1 (0.36 g) was dissolved in dry toluene (25 ml)and DMAP (0.262 g) was added. A solution of 2,4,6-trifluorophehylacetylchloride (0.45 g) in dry toluene (1 ml) was added dropwise withstirring, and a white precipitate formed. After stirring at roomtemperature for 10 minutes the reaction was stirred under reflux for 4.5hours, and then allowed to stand overnight at room temperature. Thewhite solid was filtered and washed with toluene, and the filtrateevaporated to give a brown oil, which was purified by HPLC eluting withethyl acetate:hexane 4:1 to give3-[2-(2,4,6-trifluorophenyl)acetylamino]-pyridazine-4-carboxylic acidethyl ester as a pale yellow solid (0.57 g), m.p. 135° C.

¹H NMR (CDCl₃) δ ppm: 1.40 (t,3H), 4.22 (s,2H), 4.41 (q,2H), 6.70(m,2H), 7.94 (d,1H), 9.15 (d,1H), 10.30 (bs,1H).

Step 3

The product from Step 2 (2.0 g) was dissolved in dry THF (50 ml), andsodium bis-trimethylsilylamide (17.7 ml of a 11.0M solution in THF) wasadded dropwise with stirring under nitrogen at 0° C. The reaction wasstirred for 3 hours at 0° C. and a yellow precipitate was formed. Thereaction was quenched with concentrated hydrochloric acid and thenpoured into ice water. The solid was filtered, washed with water and airdried to give6-(2,4,6-trifluorophenyl)-8H-pyrido[2,3-c]pyridazine-5,7-dione as ayellow solid (1.9 2 g), m.p. >330° C., still containing some THF, whichwas used without further purification.

¹H NMR (D₆-DMSO) δ ppm: 7.30 (m,2H), 8.10 (d,1H), 9.20 (d,1H), 11.90(bs,1H), 12.60 (s,1H).

Step 4

The product from Step 3 (0.060 g) was heated to 90° C. in phosphorusoxychloride (1 ml) for 1 hour to give a clear black solution. Themixture was cooled and the excess in phosphorus oxychloride evaporated.The residue was quenched with ice and aqueous sodium bicarbonate,extracted with ethyl acetate, the extract dried over magnesium sulphateand evaporated to give5,7-dichloro-6-(2,4,6-trifluorophenyl)-pyrido[2,3-c]pyridazine as ablack solid (0.087 g).

¹H NMR (CDCl₃) δ ppm: 6.90 (m,2H), 8.30 (d,1H), 9.75 (d,1H).

Step 4

The product from Step 3 (0.080 g) was stirred with isopropylamine (2 ml)in DCM (5 ml) at room temperature overnight and then heated to 40° C. ina sealed tube for 4 hours. The volatiles were evaporated, water wasadded and the mixture extracted with DCM. The extracts were dried overmagnesium sulphate and evaporated to give a dark brown tar, which waspurified by preparative TLC on silica gel plates eluting with ethylacetate:hexane 3:2 to give two isomers:

-   [5-chloro-6-(2,4,6-trifluoro-phenyl)-pyrido[2,3-c]pyridazin-7-yl]-isopropylamine    as a gum (0.0014 g),

¹H NMR (CDCl₃) δ ppm: 1.26 (d,6H), 4.67 (bs,1H), 4.7.5 (m,1H), 6.92-6.97(m,2H), 7.79 (d,1H), 9.24 (d,1H).

-   [7-Chloro-6-(2,4,6-trifluorophenyl)-pyrido[2,3-c]pyridazin-5-yl]-isopropylamine    (0.008 g),

¹H NMR (CDCl₃) δ ppm: 1.20 (d,6H), 3.71 (m,1H), 4.45 (bs,1H), 6.87-6.92(m,2H), 7.97 (d,1H), 9.37 (d,1H). TABLE 133 Compound Table NMR data(ppm, in CDCl₃, No. No. Compound Structure unless otherwise stated) orMpt.  3  1

1.1(d, 6H), 3.26(m, 1H), 6.84(m, 2H), 6.95 (bd, 1H), 8.67(d, 1H), 9.0(d,1H).  4  1

0.8(t, 3H), 1.27(m, 2H), 1.55(m, 2H), 2.87 (m, 2H), 6.8, 6.85(ABd, 2H);8.66, 8.99 (ABd, 2H). 14  1

129-131° C. 15  1

149-150° C. 16  1

175-177° C. 17  1

153-155° C. 22  1

0.92(m)+1.22(m)+1.55(m)(total=8H), 2.9 (m, 2H), 6.85(m, 2H), 8.78,8.96(ABd, 2H). 23  1

151-153° C. 58  1

102-104° C. 108   1

1.12(d, 3H), 3.27(m, 2H), 3.3(s, 3H), 3.5 (m, 1H), 6.8(m, 2H),8.67(d)+8.97(ABd)(total═2H) 161   1

138-140° C. 162   1

140-141° C. 219   1

3.0(s, 6H), 6.85(m, 2H), 8.65, 8.87(ABd, 2H)  3  5

157-159° C.  4  5

0.82(m, 3H), 1.22m+1.5m(total=4H), 2.82 (m, 2H), 7.1-7.47(m, 3H),8.67+9.05(ABd, 2H). 17  5

159-160° C. 20  5

166-168° C. 22  5

163-165° C. 23  5

163-165° C. 28  5

71-73° C. 108   5

1.05(d)+1.12(d)(total=3H), 3.1-3.5(m, 3H), 3.25(d)+3.32(d)(total=3H),7.1(m)+7.4 (m)(total=4H), 8.67(d, 1H), 9.06(d, 1H) 161   5

0.82(m, 4H), 3.65(m, 4H), 7.12-7.35(m, 3H), 8.66+8.87(ABd, 2H). 162   5

1.52(m, 6H), 3.3(m, 4H), 7.25(m)+7.4(m) (total═3H), 8.78+8.95(ABd, 2H).171   5

2.3(s, 3H), 2.5(m, 4H), 7.15(m, 1H), 7.37 (m, 2H), 8.75(d, 1H), 8.92(d,1H).  3  6

1.25(d, 6H), 4.62(bd, 1H), 4.75(m, 1H), 6.67 (m, 2H), 8.64(d, 1H),8.85(d, 1H).  4  6

165-167° C. 15  6

214-216° C. 17  6

156-158° C. 20  6

3.4(m, 4H), 3.6(m, 4H), 6.9(m, 2H), 8.8(d, 1H, 8.95(d, 1H). 22  6

159-160° C. 23  6

145-147° C. 58  6

165-167° C. 108   6

1.27(d, 3H), 3.3(s, 3H), 3.47(m, 2H), 4.75 (m, H), 5.1(bd, 1H), 6.92(m,2H), 8.64(d, 1H), 8.85(d, 1H). 161   6

1.9m(4H); 3.4m(4H); 6.85m(2H); 8.62d(1H); 8.85d(1H) 162   6

1.4-1.55(m, 6H), 3.35(m, 4H), 6.87(m, 2H), 8.72 (d, 1H), 8.92(d, 1H).219   6

166-168° C.  3 10

155-157° C.  4 10

159-160° C. 17 10

131-132° C. 20 10

171-173° C. 22 10

0.9(d, 3H), 0.87-1.1(m, 2H), 1.5(m, 3H), 2.87 (m, 2H), 3.87(m, 2H),7.17(m)+7.4(m)(total═3H), 8.72(d, 1H), 8.90(d, 1H). 23 10

0.87(m)+1.2(m)+1.5(m)(total=8H), 4.45 (bt, 1H), 4.5(m, 1H),7.25(m)+7.5(m)(total═3H), 8.63(d, 1H), 8.88(d, 1H). 108  10

1.25(m, 3H, 3.25(d, 3H), 3.45(m, 2H), 4.75 (m, 1H), 5.0(bt, 1H),7.22(m)+7.47(m)(total═3H), 8.64(d, 1H), 8.84(d, 1H). 161  10

177-179° C. 162  10

163-164° C.  3 11

1.16(d, 6H), 3.41(m, 1H), 6.85(dd, 2H), 7.79 (bs, 1H), 7.84(d, 1H).9.40(d, 1H). 23 11

0.79(t, 3H), 1.11(d, 3H), 1.47(m, 2H), 3.13 (m, 1H), 6.86(dd, 2H),7.79(bs, 1H), 7.84(d, 1H), 9.40(d, 1H).  3 16

1.24(d, 6H), 4.53(m, 1H), 4.73(d, 1H), 6.94 (dd, 2H), 7.67(d, 1H),9.25(d, 1H). 23 16

0.90(t, 3H), 1.20(d, 3H), 1.53(m, 2H), 4.38 (m, 1H), 4.62(d, 1H),6.95(dd, 2H), 7.63(d, 1H), 9.25(d, 1H).  3 21

1.27(d, 6H), 4.05(m, 1H), 4.90(bs, 1H), 6.92 (m, 2H), 9.55(s, 1H),9.90(s, 1H).  3 26

1.20(d, 6H), 3.71(m, 1H), 4.45(bs, 1H), 6.87-6.92 (m, 2H), 7.97(d, 1H),9.37(d, 1H).  3 31

1.25(d, 6H), 4.5(bd, 1H) 4.6(m, 1H), 7.15(t, 2H), 7.6(m, 1H), 8.625(fd,1H), 8.85(fd, 1H). 665  31

1.10(d, 6H), 3.30(m, 1H), 6.90(bd, 1H), 7.05 (t, 2H), 7.50(m, 1H),8.65(fd, 1H), 9.0(fd, 1H).  3 32

1.10(d, 6H), 4.52(m, 2H), 7.28(m, 3H), 7.47 (m, 1H), 8.52(d, 1H),8.76(d, 1H) 23 32

0.78(m, 3H), 1.07(m, 3H), 1.45(m, 2H), 4.48 (m, 2H), 7.25(m, 3H),7.50(m, 1H), 8.51(d, 1H), 8.71(d, 1H)  3 37

160-161° C. 16 37

181-183° C. 171  37

2.3(s, 3H), 2.5(m, 3H), 3.2-3.5(m, 4H),7.27(m)+7.4(m)+7.62(m)(total=3H), 8.77(d, 1H), 8.92(d, 1H). 665  37

0.92(d, 6H), 1.95(m, 1H), 3.37(m)+3.57(m) (total=2H), 4.67(bt, 1H),7.27(d)+7.5(m)+7.67(d)(total=3H), 8.62(d, 1H), 8.95(d, 1H). 678  37

1.35(m)+1.62(m)+2.15(m)(total 8H), 4.6 (bd, 1H), 4.75(m, 1H),7.3(m)+7.5(m)(total=3H), 8.67(d, 1H), 8.87(d, 1H). 833  37

2.27(s, 3H), 2.35(m, 4H), 3.42(m, 4H), 7.3-7.6 (m, 3H), 8.67(d, 1H),8.92(d, 1H).  3 43

1.10(d, 6H), 4.32(d, 1H), 4.57(m, 1H), 7.22 (m, 1H), 7.35(m, 1H),7.48(m, 1H), 7.78(m, H), 8.53(d, 1H), 8.71(d, 1H) 23 43

0.81(m, 3H), 1.10(m, 3H), 1.40(m, 2H), 4.26 (m, 1H), 4.45(m, 1H),7.25(m, 1H), 7.38(m, 1H), 7.50(m, 1H), 7.76(m, 1H), 8.52(d, 1H), 8.74(d, 1H) 685  43

0.62(m, 3H), 1.02(m, 3H), 1.32(m, 2H), 3.02 (m, 1H), 6.42(m, 1H),7.28(m, 1H), 7.46(m, 1H), 7.62(m, 1H), 7.69(m, 1H), 9.02(d, 1H), 9.10(d, 1H).  3 103 

127-128° C.  5 103 

138-140° C. 12 103 

106-108° C. 14 103 

120-121° C. 15 103 

153-154° C. 23 103 

101-102° C. 58 103 

99-100° C. 92 103 

1.07(t, 3H), 1.57(s, 3H), 3.52(s, 2H), 3.72 (q, 2H), 4.85(m, 2H),6.85(m, 2H), 8.8(d, 1H), 9.0(d, 1H). 161  103 

148-150° C. 171  103 

167-160° C. 2651  103 

100-101° C. 2660  103 

1.3(d, 3H), 1.4(d, 3H), 3.9(m, 1H), 6.95-7.6 (m, 4H), 8.75(m, 1H),9.05(m, 1H). 2671  103 

123-124° C. 2706  103 

0.8(m, 6H), 1.72(m, 1H), 2.6(m, 2H), 7.02-747 (m, 4H), 8.6(d, 1H),8.92(d, 1H). 3313  103 

1.25(m, 6H), 4.5(bd, 1H), 4.67(m, 1H), 7.25(m)+7.5(m)(total=2H), 8.58(d,1H), 8.83(d, 1H). 3471  103 

151-152° C. 43704   103 

133-135° C. (diastereoisomer 1) 43704   103 

137-139° C. (diastereoisomer 2) 43715   103 

118-119° C. 43750   103 

0.80(d)+0.83(d)(total=6H), 1.72(m, 1H), 2.65(m, 2H), 7.1-7.3(m)+7.35,7.6(d)(total =3H), 8.6(d, 1H), 8.92(d, 1H).  3 117 

1.25(d, 6H), 4.54(m, 1H), 4.67(bs, 1H), 6.90 (m, 2H), 9.40(s, 1H),9.50(s, 1H).  3 122 

1.27(d, 6H), 4.70-4.85(bs+m, 2H), 6.95 (m, 3H), 8.02(d, 1H), 9.22(d,1H). 15 127 

218-220° C.  1 128 

4.03(s, 5H), 6.74(t, 2H), 8.43(d, 1H), 8.61 (d, 1H) 10.9(s, 1H).  6 128 

162-163° C. 12 128 

158-159° C. 13 128 

1.48(t, 3H), 4.52(q, 2H), 6.73(d, 1H), 8.75 (d, 1H). 25 128 

1.45(t, 3H), 3.90(s, 2H), (4.45(q, 2H), 6.75 (m, 2H), 9.45(s1H),10.60(s, 1H), 11.1(bs, 1H). 37 128 

1.40(t, 3H), 4.22(s, 2H), 4.41(q, 2H), 6.70 (m, 2H), 7.94(d, 1H),9.15(d, 1H), 10.30(bs, 1H).  1 129 

(d⁶-DMSO) 7.25(t, 2H), 8.6(fd, 1H), 8.7(fd, 1H), 12.6(s, 1H).  6 129 

>220° C.  9 129 

250-252° C. 11 129 

258° C. 12 129 

>200° C. 13 129 

(CD₃OD) 6.83(2d, 2H), 7.44(d, 1H), 9.00 (d, 1H). 25 129 

(d⁶-DMSO) 7.25(m, 2H), 9.17(s, 1H), 9.47 (s, 1H), 12.30(bs, 1H). 37 129 

(D₆-DMSO) 7.30(m, 2H), 8.10(d, 1H), 9.20 (d, 1H), 11.90(bs, 1H),12.60(s, 1H).  1 130 

139-141° C.  6 130 

154-155° C.  9 130 

7.21(m, 1H), 7.28(m, 2H), 7.48(m, 1H), 8.95(d, 1H), 9.08(d, 1H). 11 130 

7.18(d, 1H), 7.29(m, 1H), 7.41(t, 1H), 7.69(dd, 1H), 9.00(d, 1H),9.09(d, 1H). 12 130 

159-160° C. 13 130 

6.92(m, 2H), 8.11(d, 1H), 9.71(d, 1H). 25 130 

6.90(m, 2H), 9.80(s, 1H), 10.0(s, H). 37 130 

6.90(m, 2H), 8.30(d, 1H), 9.75(d, 1H).  1 131 

120-121° C.  6 131 

7.27(m)+7.55(m)(total=3H), 9.07(d, 1H), 9.2(d, 1H). 12 131 

7.45(m)+7.67(d)(total=3H), 9.07(d, 1H), 9.2 (d, 1H).

EXAMPLE 6

This Example illustrates the fungicidal properties of the compounds ofthe general formula (1).

Compounds were tested in a leaf disk assay, with methods describedbelow. Test compounds were dissolved in DMSO, and diluted into water to200 ppm.

Plasmopara viticola (downy mildew of grapevine): grapevine leaf diskswere placed on agar in a 24-well plate and sprayed a solution of thetest compound. After allowing to dry completely, for between 12 and 24hours, the leaf disks were inoculated with a spore suspension of thefungus. After appropriate incubation the activity of a compound wasassessed seven days after inoculation as preventive fungicidal activity.

Phzytophthora infestans (late blight of potato on tomato): tomato leafdisks were placed on water agar in a 24-well plate and sprayed with asolution of the test compound. After allowing to dry completely, forbetween 12 and 24 hours, the leaf disks were inoculated with a sporesuspension of the fungus. After appropriate incubation the activity of acompound was assessed four days after inoculation as preventivefungicidal activity.

Erysiphe graminis f.sp. hordei (barley powdery mildew): barley leafsegments were placed on agar in a 24-well plate and sprayed with asolution of the test compound. After allowing to dry completely, forbetween 12 and 24 hours, the leaf disks were inoculated with a sporesuspension of the fungus. After appropriate incubation the activity of acompound was assessed four days after inoculation as preventivefungicidal activity.

Erysiphe graminis f.sp. tritici (wheat powdery mildew): wheat leafsegments were placed on agar in a 24-well plate and sprayed with asolution of the test compound. After allowing to dry completely, forbetween 12 and 24 hours, the leaf disks were inoculated with a sporesuspension of the fungus. After appropriate incubation the activity of acompound was assessed four days after inoculation as preventivefungicidal activity.

Puccinia recondita f.sp. tritici (wheat brown rust): wheat leaf segmentswere placed on agar in a 24-well plate and sprayed with a solution ofthe test compound. After allowing to dry completely, for between 12 and24 hours, the leaf disks were inoculated with a spore suspension of thefungus. After appropriate incubation the activity of a compound wasassessed nine days after inoculation as preventive fungicidal activity.

Septoria nodorum (wheat glume blotch): wheat leaf segments were placedon agar in a 24-well plate and sprayed with a solution of the testcompound. After allowing to dry completely, for between 12 and 24 hours,the leaf disks were inoculated with a spore suspension of the fungus.After appropriate incubation the activity of a compound was assessedfour days after inoculation as preventive fungicidal activity.

Pyrenophora teres (barley net blotch): barley leaf segments were placedon agar in a 24-well plate and sprayed with a solution of the testcompound. After allowing to dry completely, for between 12 and 24 hours,the leaf disks were inoculated with a spore suspension of the fungus.After appropriate incubation the activity of a compound was assessedfour days after inoculation as preventive fungicidal activity.

Pyricularia oryzae (rice blast): rice leaf segments were placed on agarin a 24-well plate and sprayed with a solution of the test compound.After allowing to dry completely, for between 12 and 24 hours, the leafdisks were inoculated with a spore suspension of the fungus. Afterappropriate incubation the activity of a compound was assessed four daysafter inoculation as preventive fungicidal activity.

Botrytis cinerea (grey mould): bean leaf disks were placed on agar in a24-well plate and sprayed with a solution of the test compound. Afterallowing to dry completely, for between 12 and 24 hours, the leaf diskswere inoculated with a spore suspension of the fungus. After appropriateincubation the activity of a compound was assessed four days afterinoculation as preventive fungicidal activity.

The following compounds gave greater than 60% control of disease:

Plasinopara viticola, Compounds 4 (1), 20 (1), 23 (5), 58 (6), 162 (6),22 (10), 23 (10), 6 (120), 12 (120);

Phlytophthora infestans, Compounds 3 (1), 58 (5), 162 (10), 3 (103);

Eiysiphe grarninis f.sp. hordei, Compounds 3 (1), 14 (1), 15 (1), 16(1), 17 (1), 22 (1), 23 (1), 58 (1), 108 (1), 161 (1), 162 (1), 3 (5), 4(5), 17 (5), 20 (5), 22 (5), 23 (5), 28 (5), 58 (5), 108 (5), 162 (5),171 (5), 3 (6), 4 (6), 15 (6), 20 (10), 23 (10), 161 (10), 665 (31), 23(32), 3 (37), 16 (37), 171 (37), 665 (37), 678 (37), 3 (43), 23 (43),685 (43), 3 (103), 12 (103), 23 (103), 58 (103), 92 (103), 2651 (103),2660 (103), 2671 (103), 23844 (103) diastereoisomer 1, 23844 (103)diastereoisomer 2, 23855 (103), 23890 (103;

Erysiphe graminis f.sp. tritici, Compounds 3 (1), 4 (1), 15 (1), 16 (1),22 91), 23 (1), 58 (1), 108 (1), 162 (1), 219 (1), 58 95), 161 (5), 22(6), 162 (10), 3 (31), 16 (37), 665 (37), 3 (103), 12 (103), 23 (103),58 (103), 92 (103), 2651 (103), 2660 (103), 2671 (103), 23844 (103)diastereoisomer 1, 23844 (103) diastereoisomer 2, 23855 (103), 23890(103);

Puccinia recondita f.sp. tritici, Compounds 3 (1), 14 91), 15 (1), 16(1), 17 (1), 23 (1), 58 (1), 108 (1), 161 (1), 162 (1), 4 (5), 17 (5),23 (5), 28 (5), 58 (5), 108 (5), 162 (10), 3 (31), 16 (37), 665 (37),678 (37), 3 (103), 12 (103), 23 (103), 58 (103), 92 (103), 2651 (103),2660 (103), 2671 (103), 23844 (103) diastereoisomer 1, 23855 (103),23890 (103);

Septoria nodorum, Compounds 391), 15 (1), 16 (1), 17 (1), 23 (1), 58(1), 58 95), 161 (5), 22 (6), 665 (37), 685 (43), 12 (103), 23 (103), 58(103), 2660 (103), 2671 (103), 23844 (103) diastereoisomer 1, 23855(103), 23890 (103);

Pyrenophora teres, Compounds 3 (1), 14 (1), 15 (1), 16 (1), 17 (1), 23(1), 58 (1), 161 (1), 3 (5), 20 (5), 16 (37), 665 (37), 3 (103), 12(103), 23 (103), 58 (103), 2651 (103), 2660 (103), 2671 (103), 23844(103) diastereoisomer 1, 23855 (103), 23890 (103);

Pyricularia oryzae, Compounds 3 (1), 4 (1), 14 (1), 15 (1), 16 (1), 17(1), 20 (1), 23 (1), 58 (1), 108 (1), 161 (1), 3 (5), 4 (5), 20 (5), 23(5), 58 (5), 108 (5), 3 (6), 22 (6), 219 (6), 22 (10), 3 (32), 3 (37),16 (37), 678 (37), 3 (43), 3 (103), 12 (103), 23 (103), 58 (103), 92(103), 171 (103), 2651 (103), 2669 (103), 2671 (103), 23844 (103)diastereoisomer 1, 23844 (103) diastereoisomer 2, 23855 (103), 23890(103);

Botrytis cinerea, Compounds 4 (1), 14 (1), 15 (1), 16 (1), 17 (1), 22(1), 58 (1), 108 (1), 4 (5), 22 (5), 28 (5), 58 (5), 108 (5), 162 (5), 3(6), 3 (10), 16 (37), 678 (37), 23 (103), 92 (103), 2651 (103), 2660(103), 23844 (103) diastereoisomer 2, 23855 (103), 23890 (103).

1. The compound of the general formula (1):

wherein W and X, W and Z, X and Y or Y and Z are N and the other two areCR⁸; R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl; R and R²are independently H, halo, C₁₋₈ alkyl, C₁₋₈ alkoxy, C₁₋₈ alkylthio, C₂-galkenyl, C₂₋₈ alkynyl, cyano or NR³R⁴, provided that at least one of Rand R² is NR³R⁴; R¹ is halo, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl,C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, C₁₋₈ alkoxy, C₁₋₈alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy,heteroarylthio, aryl(C₁₋₄)alkyl, aryl(C₁₋₄)alkoxy,heteroaryl(C₁₋₄)alkyl, heteroaryl(C₁₋₄)alkoxy, aryl(C₁₋₄)alkylthio,heteroaryl(C₁₋₄)alkylthio, morpholino, piperidino or pyrrolidino; R³ andR⁴ are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl,aryl(C₁₋₈)alkyl, C₃₋₉ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl,heteroaryl, heteroaryl(C₁₋₈)alkyl, NR⁵R⁶, provided that not both R³ andR⁴ are H or NR⁵R⁶, or R³ and R⁴ together form a C₃₋₇ alkylene or C₃₋₇alkenylene chain optionally substituted with one or more C₁₋₄ alkyl orC₁₋₄ alkoxy groups, or, together with the nitrogen atom to which theyare attached, R³ and R⁴ form a morpholine, thiomorpholine,thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazineor piperazine N—(C₁₋₄)alkyl (especially N-methyl) ring; and R⁵ and R⁶are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl,aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, heteroarylor heteroaryl(C₈)alkyl; any of the foregoing alkyl, alkenyl, alkynyl orcycloalkyl groups or moieties (other than for R⁸) being optionallysubstituted with halogen, cyano, C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆alkoxycarbonyl, C₁₋₆ haloalkoxy, C₁₋₆ alkylthio, tri(C₁₋₄)alkylsilyl,C₁₋₆ alkylamino or C₁₋₆ dialkylamino, any of the foregoing morpholine,thiomorpholine, piperidine, piperazine and pyrrolidine rings beingoptionally substituted with C₁₋₄ alkyl (especially methyl), and any ofthe foregoing aryl or heteroaryl groups or moieties being optionallysubstituted with one or more substituents selected from halo, hydroxy,mercapto, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ alkoxy, C₂₋₆alkenyloxy, C₂₋₆ alkynyloxy, halo(C₁₋₆)alkyl, halo(C₁₋₆)alkoxy, C₁₋₆alkylthio, halo(C₁₋₆)alkylthio, hydroxy(C₁₋₆)alkyl, C₁₋₄alkoxy(C₁₋₆)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenoxy,benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato,nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″, —CONR′″R″″, —SO₂R′″, —OSO₂R′″,—COR′″, —CR′″═NR″″, or —N═CR′″R″″, in which R′″ and R″″ areindependently hydrogen, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy,halo(C₁₋₄)alkoxy, C₁₋₄ alkythio, C₃₋₆ cycloalkyl, C₃₋₆cycloalkyl(C₁₋₄)alkyl, phenyl or benzyl, the phenyl and benzyl groupsbeing optionally substituted with halogen, C₁₋₄ alkyl or C₁₋₄ alkoxy. 2.A compound according to claim 1 wherein W and Z are N and X and Y areCH.
 3. A compound according to claim 1 or 2 wherein R² is NR³R⁴.
 4. Acompound according to claim 3 wherein R is halo.
 5. A compound accordingto any one of the preceding claims wherein R³ is C₁₋₈ alkyl,halo(C₁₋₈)alkyl, hydroxy(C₁₋₈)alkyl, C₁₋₄ alkoxy(C₁₋₈)alkyl, C₁₋₄alkoxyhalo(C₁₋₈)alkyl, tri(C₁₋₄)alkylsilyl(C₁₋₆b)alkyl, C₁₋₄alkylcarbonyl(C₁₋₈)alkyl, C₁₋₄ alkylcarbonylhalo(C₁₋₈)alkyl,phenyl(₁₋₄)alkyl, C₂₋₈ alkenyl, halo(C₂₋₈)alkenyl, C₂₋₈ alkynyl, C₃₋₈cycloalkyl optionally substituted with chloro, fluoro or methyl, C₃₋₈cycloalkyl(C₁₋₄)alkyl, phenylamino, piperidino or morpholino, the phenylring of phenylalkyl or phenylamino being optionally substituted withone, two or three substituents selected from halo, C₁₋₄ alkyl,halo(C₁₋₄)alkyl, C₁₋₄ alkoxy and halo(C₁₋₄)alkoxy; and R⁴ is H, C₁₋₄alkyl, halo(C₁₋₄)alkyl or amino, or R³ and R⁴ together form a C₃₋₇alkylene or alkenylene chain optionally substituted with methyl, or,together with the nitrogen atom to which they are attached, R³ and R⁴form a morpholine, thiomorpholine, thiomorpholine S-oxide orthiomorpholine S-dioxide ring or a piperazine or piperazineN—(C₁₋₄)alkyl (especially N-methyl) ring, in which the morpholine orpiperazine rings are optionally substituted with methyl.
 6. A compoundaccording to any one of the preceding claims wherein R¹ is phenyloptionally substituted with from one to five halogen atoms or with fromone to three substituents selected from halo, C₁₋₄ alkyl,halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkoxy, pyridyl optionallysubstituted with from one to four halogen atoms or with from one tothree substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄alkoxy or halo(C₁₋₄)alkoxy, 2- or 3-thienyl optionally substituted withfrom one to three halogen atoms or with from one to three substituentsselected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy orhalo(C₁₋₄)alkoxy, or piperidino or morpholino both optionallysubstituted with one or two methyl groups.
 7. A compound according toclaim 6 wherein R¹ is 2,6-difluorophenyl, 2-fluoro-6-chlorophenyl,2,5,6-trifluorophenyl, 2,4,6-trifluorophenyl,2,6-difluoro-4-methoxyphenyl or pentafluorophenyl.
 8. A compoundaccording to claim 1 wherein W and X, W and Z, X and Y or Y and Z are Nand the other two are CR⁸; R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄ alkoxy orhalo(C₁₋₄)alkyl; one of R and R² (preferably R²) is NR³R⁴ and the otheris halo; R¹ is halo, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, C₃₋₈cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, C₁₋₈ alkoxy, C₁₋₈ alkylthio,aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy, heteroarylthio,aryl(C₁₋₄)alkyl, aryl(C₁₋₄)alkoxy, heteroaryl(C₁₋₄)alkyl,heteroaryl(C₁₋₄)alkoxy, aryl(C₁₋₄)alkylthio, heteroaryl(C₁₋₄)alkylthio,morpholino, piperidino or pyrrolidino; R³ and R⁴ are independently H,C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl, aryl(C₁₋₈)alkyl, C₃₋₈cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, heteroaryl,heteroaryl(C₁₋₈)alkyl, NR⁵R⁶, provided that not both R³ and R⁴ are H orNR⁵R⁶, or R³ and R⁴ together form a C₃₋₇ alkylene or C₃₋₇ alkenylenechain optionally substituted with one or more C₁₋₄ alkyl or C₁₋₄ alkoxygroups, or, together with the nitrogen atom to which they are attached,R³ and R⁴ form a morpholine, thiomorpholine, thiomorpholine S-oxide orthiomorpholine S-dioxide ring or a piperazine or piperazineN—(C₁₋₄)alkyl (especially N-methyl) ring; and R⁵ and R⁶ areindependently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl,aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, heteroarylor heteroaryl(C₁₋₈)alkyl; any of the foregoing alkyl, alkenyl, alkynylor cycloalkyl groups or moieties (other than for R⁸) being optionallysubstituted with halogen, cyano, C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆alkoxycarbonyl, C₁₋₆ haloalkoxy, C₁₋₆ alkylthio, tri(C₁₋₄)alkylsilyl,C₁₋₆ alkylamino or C₁₋₆ dialkylamino, any of the foregoing morpholine,thiomorpholine, piperidine, piperazine and pyrrolidine rings beingoptionally substituted with C₁₋₄ alkyl (especially methyl), and any ofthe aryl, heteroaryl, aryloxy or heteroaryl groups being optionallysubstituted with one or more substituents selected from halo, hydroxy,mercapto, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl, C₁₋₆ alkoxy, C₂₋₆alkenyloxy, C₂₋₆ alkynyloxy, halo(C₁₋₆)alkyl, halo(C₁₋₆)alkoxy, C₁₋₆alkylthio, halo(C₁₋₆)alkylthio, hydroxy(C₁₋₆)alkyl, C₁₋₄alkoxy(C₁₋₆)alkyl, C₃₋₆ cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenoxy,benzyloxy, benzoyloxy, cyano, isocyano, thiocyanato, isothiocyanato,nitro, —NR′″ R″″, —NHCOR′″, —NHCONR′″ R″″, —CONR′″ R″″, —SO₂R′″,—OSO₂R′″, —COR′″, —CR′″═NR″″ or —N═CR′″ R″″, in which R′″ and R″″ areindependently hydrogen, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy,halo(C₁₋₄)alkoxy, C₁₋₄ alkylthio, C₃₋₆ cycloalkyl, C₃₋₆cycloalkyl(C₁₋₄)alkyl, phenyl or benzyl, the phenyl and benzyl groupsbeing optionally substituted with halogen, C₁₋₄ alkyl or C₁₋₄ alkoxy. 9.A compound according to claim 1 wherein W and X, W and Z, X and Y or Yand Z are N and the other two are CR⁸; R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄alkoxy or halo(C₁₋₄)alkyl; one of R and R² (preferably R²) is NR³R⁴ andthe other is halo; R¹ is halo, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl,C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, C₁₋₈ alkoxy, C₁₋₈alkylthio, aryl, aryloxy, arylthio, heteroaryl, heteroaryloxy,heteroarylthio, aryl(C₁₋₄)alkyl, aryl(C₁₋₄)alkoxy,heteroaryl(C₁₋₄)alkyl, heteroaryl(C₁₋₄)alkoxy, aryl(C₁₋₄)alkylthio,heteroaryl(C₁₋₄)alkylthio, morpholino, piperidino or pyrrolidino; R³ isC₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₂₋₄ alkenyl, C₃₋₆ cycloalkyl, C₃₋₆cycloalkyl(C₁₋₄)alkyl or phenylamino in which the phenyl ring isoptionally substituted with one, two or three substituents selected fromhalo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy and halo(C₁₋₄)alkoxy; andR⁴ is H, C₁₋₄ alkyl or amino, or R³ and R⁴ together form a C₄₋₆ alkylenechain optionally substituted with C₁₋₄ alkyl or C₁₋₄ alkoxy, or,together with the nitrogen atom to which they are attached, R³ and R⁴form a morpholine, thiomorpholine, thiomorpholine S-oxide orthiomorpholine S-dioxide ring or a piperazine or piperazineN—(C₁₋₄)alkyl (especially N-methyl) ring; any of the alkyl, alkenyl,alkynyl or cycloalkyl groups or moieties (other than for R⁸) beingoptionally substituted with halogen, cyano, C₁₋₆ alkoxy, C₁₋₆alkylcarbonyl, C₁₋₆ alkoxycarbonyl, C₁₋₆ haloalkoxy, C₁₋₆ alkylthio,tri(C₁₋₄)alkylsilyl, C₁₋₆ alkylamino or C₁₋₆ dialkylamino, any of theforegoing morpholine, thiomorpholine, piperidine, piperazine andpyrrolidine rings being optionally substituted with C₁₋₄ alkyl(especially methyl), and any of the aryl or heteroaryl groups ormoieties being optionally substituted with one or more substituentsselected from halo, hydroxy, mercapto, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆alkynyl, C₁₋₆ alkoxy, C₂₋₆ alkenyloxy, C₂₋₆ alkynyloxy, halo(C₁₋₆)alkyl,halo(C₁₋₆)alkoxy, C₁₋₆ alkylthio, halo(C₁₋₆)alkylthio,hydroxy(C₁₋₆)alkyl, C₁₋₄ alkoxy(C₁₋₆)alkyl, C₃₋₆ cycloalkyl, C₃₋₆cycloalkyl(C₁₋₄)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano,thiocyanato, isothiocyanato, nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″,—CONR′″R″″, —SO₂R′″, —OSO₂R′″, —COR′″, —CR′″═NR″″ or —N═CR′″ R″″, inwhich R′″ and R″″ are independently hydrogen, C₁₋₄ alkyl,halo(C₁₋₄)alkyl, C₁₋₄ alkoxy, halo(C₁₋₄)alkoxy, C₁₋₄ alkylthio, C₃₋₆cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenyl or benzyl, the phenyl andbenzyl groups being optionally substituted with halogen, C₁₋₄ alkyl orC₁₋₄ alkoxy.
 10. A compound according to claim 1 wherein W and X, W andZ, X and Y or Y and Z are N and the other two are CR⁸; R⁸ is H, halo,C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl; R and R² are independentlyH, halo, C₁₋₈ alkyl, C₁₋₈ alkoxy, C₁₋₈ alkylthio, C₂₋₈ alkenyl, C₂₋₈alkynyl, cyano or NR³R⁴, provided that at least one of R and R²(preferably R²) is NR³R⁴; R¹ is optionally substituted phenyl; R³ and R⁴are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl,aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl,heteroaryl, heteroaryl(C₁₋₈)alkyl, NR⁵R⁶, provided that not both R³ andR⁴ are H or NR⁵R⁶, or R³ and R⁴ together form a C₃₋₇ alkylene or C₃₋₇alkenylene chain optionally substituted with one or more C₁₋₄ alkyl orC₁₋₄ alkoxy groups, or, together with the nitrogen atom to which theyare attached, R³ and R⁴ form a morpholine, thiomorpholine,thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazineor piperazine N—(C₁₋₄)alkyl (especially N-methyl) ring; and R⁵ and R⁶are independently H, C₁₋₈ alkyl, C₂₋₈ alkenyl, C₂₋₈ alkynyl, aryl,aryl(C₁₋₈)alkyl, C₃₋₈ cycloalkyl, C₃₋₈ cycloalkyl(C₁₋₆)alkyl, heteroarylor heteroaryl(C₁₋₈)alkyl; any of the alkyl, alkenyl, alkynyl orcycloalkyl groups or moieties (other than for R⁸) being optionallysubstituted with halogen, cyano, C₁₋₆ alkoxy, C₁₋₆ alkylcarbonyl, C₁₋₆alkoxycarbonyl, C₁₋₆ haloalkoxy, C₁₋₆ alkylthio, tri(C₁₋₄)alkylsilyl,C₁₋₆ alkylamino or C₁₋₆ dialkylamino, any of the foregoing morpholine,thiomorpholine, piperidine, piperazine and pyrrolidine rings beingoptionally substituted with C₁₋₄ alkyl (especially methyl), and any ofthe aryl or heteroaryl groups or moieties, including the phenyl group ofR¹, being optionally substituted with one or more substituents selectedfrom halo, hydroxy, mercapto, C₁₋₆ alkyl, C₂₋₆ alkenyl, C₂₋₆ alkynyl,C₁₋₆ alkoxy, C₂₋₆ alkenyloxy, C₂₋₆ alkynyloxy, halo(C₁₋₆)alkyl,halo(C₁₋₆)alkoxy, C₁₋₆ alkylthio, halo(C₁₋₆)alkylthio,hydroxy(C₁₋₆)alkyl, C₁₋₄ alkoxy(C₁₋₆)alkyl, C₃₋₆ cycloalkyl, C₃₋₆cycloalkyl(C₁₋₄)alkyl, phenoxy, benzyloxy, benzoyloxy, cyano, isocyano,thiocyanato, isothiocyanato, nitro, —NR′″R″″, —NHCOR′″, —NHCONR′″R″″,—CONR′″R″″, —SO₂R′″, —OSO₂R′″, —COR′″, —CR′″═NR″″ or —N—CR′″R″″, inwhich R′″ and R″″ are independently hydrogen, C₁₋₄ alkyl,halo(C₁₋₄)alkyl, C₁₋₄ alkoxy, halo(C₁₋₄)alkoxy, C₁₋₄ alkylthio, C₃₋₆cycloalkyl, C₃₋₆ cycloalkyl(C₁₋₄)alkyl, phenyl or benzyl, the phenyl andbenzyl groups being optionally substituted with halogen, C₁₋₄ alkyl orC₁₋₄ alkoxy.
 11. A compound according to claim 1 wherein W and X, W andZ, X and Y or Y and Z are N and the other two are CR⁸; R⁸ is H, halo,C₁₋₄ alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkyl; R is H, halo, C₁₋₄ alkyl),C₁₋₄ alkoxy or cyano; R¹ is phenyl optionally substituted with from oneto five halogen atoms or with from one to three substituents selectedfrom halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkoxy,pyridyl optionally substituted with from one to four halogen atoms orwith from one to three substituents selected from halo, C₁₋₄ alkyl,halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkoxy, 2- or 3-thienyloptionally substituted with from one to three halogen atoms or with fromone to three substituents selected from halo, C₁₋₄ alkyl,halo(C₁₋₄)alkyl, C₁₋₄ alkoxy or halo(C₁₋₄)alkoxy, or piperidino ormorpholino both optionally substituted with one or two methyl groups; R²is NR³R⁴; R³ is C₁₋₈ alkyl, halo(C₁₋₈)alkyl, hydroxy(C₁₋₈)alkyl, C₁₋₄alkoxy(C₁₋₈)alkyl, C₁₋₄ alkoxyhalo(C₁₋₈)alkyl,tri(C₁₋₄)alkylsilyl(C₁₋₆)alkyl, C₁₋₄ alkylcarbonyl(C₁₋₈)alkyl, C₁₋₄alkylcarbonylhalo(C₁₋₈)alkyl, phenyl(₁₋₄)alkyl, C₂₋₈ alkenyl,halo(C₂-s)alkenyl, C₂₋₈ alkynyl, C₃₋₈ cycloalkyl optionally substitutedwith chloro, fluoro or methyl, C₃₋₈ cycloalkyl(C₁₋₄)alkyl, phenylamino,piperidino or morpholino, the phenyl ring of phenylalkyl or phenylaminobeing optionally substituted with one, two or three substituentsselected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy andhalo(C₁₋₄)alkoxy; and R⁴ is H, C₁₋₄ alkyl, halo(C₁₋₄)alkyl or amino, orR³ and R⁴ together form a C₃₋₇ alkylene or C₃₋₇ alkenylene chainoptionally substituted with methyl, or, together with the nitrogen atomto which they are attached, R³ and R⁴ form a morpholine, thiomorpholine,thiomorpholine S-oxide or thiomorpholine S-dioxide ring or a piperazineor piperazine N—(C₁₋₄)alkyl (especially N-methyl) ring, in which themorpholine or piperazine rings are optionally substituted with methyl12. A compound according to claim 1 wherein W and X, W and Z, X and Y orY and Z are N and the other two are CR⁸; R⁸ is H, halo, C₁₋₄ alkyl, C₁₋₄alkoxy or halo(C₁₋₄)alkyl; R is halo; R¹ is phenyl optionallysubstituted with from one to five halogen atoms or with from one tothree substituents selected from halo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄alkoxy or halo(C₁₋₄)alkoxy; R² is NR³R⁴; R³ is C₁₋₄ alkyl,halo(C₁₋₄)alkyl, C₂₋₄ alkenyl, C₃₋₆ cycloalkyl, C₃₋₆cycloalkyl(C₁₋₄)alkyl or phenylamino in which the phenyl ring isoptionally substituted with one, two or three substituents selected fromhalo, C₁₋₄ alkyl, halo(C₁₋₄)alkyl, C₁₋₄ alkoxy and halo(C₁₋₄)alkoxy; andR⁴ is H, C₁₋₄ alkyl or amino, or R³ and R⁴ together form a C₄₋₆ alkylenechain optionally substituted with methyl, or, together with the nitrogenatom to which they are attached, R³ and R⁴ form a morpholine ring.
 13. Aprocess for preparing a compound of the general formula (1) according toclaim 1 wherein one of R and R² is chloro or fluoro and the other isNR³R⁴ and W, X, Y, Z, R¹, R³ and R⁴ are as defined in claim 1, whichcomprises reacting an amine of the general formula NR³R⁴ with a compoundof the general formula (6) or (13):


14. The intermediate chemicals having the general formulae (4), (5), (6)and (13):

wherein W, X, Y, Z and R¹ are as defined in claim 1 and R⁷ is C₁₋₄alkyl.
 15. A plant fungicidal composition comprising a fungicidallyeffective amount of a compound as defined in claim 1 and a suitablecarrier or diluent therefor.
 16. A method of combating or controllingphytopathogenic fungi which comprises applying to a plant, to a seed ofa plant, to the locus of the plant or seed or to soil or to any otherplant growth medium, a fungicidally effective amount of a compoundaccording to claim 1 or a composition according to claim 15.